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19 results on '"Animalerie centrale (Plate-forme)"'

1. The Spatial Heterogeneity of the Gut Limits Predation and Fosters Coexistence of Bacteria and Bacteriophages

Author: Luisa De Sordi, Thierry Pedron, Claudia Eberl, Lorenzo Chaffringeon, Quentin Lamy-Besnier, Pascal Campagne, Marion Bérard, Laurent Debarbieux, Bärbel Stecher, Marta Lourenço, Bactériophage, bactérie, hôte - Bacteriophage, bacterium, host, Institut Pasteur [Paris], Collège doctoral [Sorbonne universités], Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Descartes - Paris 5 (UPD5), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Max von Pettenkofer-Institut for Hygiene and Medical Microbiology, Ludwig-Maximilians-Universität München (LMU), Animalerie centrale (Plate-forme), German Center for Infection Research, Partnersite Munich (DZIF), Institut Carnot Pasteur Maladie Infectieuse ANR-11-CARN-017-01, M.L. is part of the Pasteur - Paris University (PPU) International PhD Program. M.L. is funded by Institut Carnot Pasteur Maladie Infectieuse (ANR 11-CARN 017-01). L.D.S. is funded by a Roux-Cantarini fellowship from the Institut Pasteur (Paris, France). L.C. is funded by a PhD fellowships from the Ministère de l’Enseignement Supérieur et de la Recherche, France, École Doctorale n°394. Q.L.-B. is funded by École Doctorale FIRE - Program Bettencourt. B.S. is supported by the German Center of Infection Research (DZIF), the Center for Gastrointestinal Microbiome Research (CEGIMIR), the DFG, Germany, Priority Programme SPP1656 (STE 1971/4-2 and STE 1971/6-1), and the Collaborative Research Center CRC 1371., We thank Harald Brüssow for critically reading the manuscript and Jorge Moura de Sousa for valuable discussion and opinion on early versions of the manuscript. We thank Dwayne Roach and Anne Chevallereau for valuable discussions. We thank Sean Benler for kindly sharing the comprehensive HMM database of Ig-like domains identified on Pfam database. We thank the members of the Centre for Gnotobiology Platform of the Institut Pasteur (Thierry Angélique, Eddie Maranghi, Martine Jacob, and Marisa Gabriela Lopez Dieguez) for their help with the animal work. We thank Cédric Fund for 16S libraries and sequencing from the Biomics Platform, C2RT, Institut Pasteur, Paris, France, supported by France Génomique (ANR-10-INBS-09-09) and IBISA., Institut Pasteur [Paris] (IP), Collège Doctoral, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Cova Rodrigues, Ana
Subjects: Male, Phage therapy, enteroaggregative, medicine.medical_treatment, viruses, [SDV]Life Sciences [q-bio], murine intestine, Gut flora, medicine.disease_cause, gnotobiotic mice, Microbiology, Predation, 03 medical and health sciences, Feces, Mice, 0302 clinical medicine, Virology, medicine, Escherichia coli, microbiota, Animals, Germ-Free Life, Bacteriophages, mucosa, Ecosystem, intestinal microbes, 030304 developmental biology, 0303 health sciences, Mucous Membrane, Oligo mouse microbiota, biology, Bacteria, Ecological dynamics, gut biogeography, biology.organism_classification, Spatial heterogeneity, Gastrointestinal Microbiome, [SDV] Life Sciences [q-bio], Gastrointestinal Tract, Mice, Inbred C57BL, Models, Animal, Microbial Interactions, Parasitology, Female, 030217 neurology & neurosurgery
Abstract: International audience; The ecological dynamics underlying the coexistence between antagonistic populations of bacteria and their viruses, bacteriophages (phages), in the mammalian gut microbiota remain poorly understood. We challenged a murine synthetic bacterial community with phages to study the factors allowing phages-bacteria coexistence. Coexistence was not dependent on the development of phage-resistant clones nor on the ability of phages to extend their host range. Instead, our data suggest that phage-inaccessible sites in the mucosa serve as a spatial refuge for bacteria. From there, bacteria disseminate in the gut lumen where they are predated by luminal phages fostering the presence of intestinal phage populations. The heterogeneous biogeography of microbes contributes to the long-term coexistence of phages with phage-susceptible bacteria. This observation could explain the persistence of intestinal phages in humans as well as the low efficiency of oral phage therapy against enteric pathogens in animal models and clinical trials.
Published: 2020

2. Bread Feeding Is a Robust and More Physiological Enteropathogen Administration Method Compared to Oral Gavage

Author: Petra Dersch, Anne Derbise, Marta Garcia-Lopez, Rémi Beau, Hebert Echenique-Rivera, Myriam Mattei, Hugo Varet, Javier Pizarro-Cerdá, Yersinia, Institut Pasteur [Paris] (IP), Animalerie centrale (Plate-forme), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), This work was supported by a grant from the Agence Nationale de la Recherche (ANR-15-CE15-0017 StopBugEntry to J.P.-C.) and an Erasmus Plus fellowship (to M.G.-L.)., ANR-15-CE15-0017,StopBugEntry,Identification des nouvelles molécules cellulaires cibles pour combattre les infections bactériennes(2015), Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and University of Münster
Subjects: 0301 basic medicine, Yersinia Infections, Gastrointestinal Diseases, [SDV]Life Sciences [q-bio], 030106 microbiology, Immunology, Administration, Oral, Yersinia, Microbiology, Feeding Methods, 03 medical and health sciences, Mice, Oral administration, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, oral infection, medicine, Yersinia pseudotuberculosis, Animals, Esophagus, Spotlight, Yersinia enterocolitica, enteropathogen, 2. Zero hunger, biology, Stomach, pathogenesis, Bread, Bacterial Infections, biology.organism_classification, Animal Feed, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Disease Models, Animal, 030104 developmental biology, Infectious Diseases, medicine.anatomical_structure, bread feeding, Parasitology, Lymph, Bacteria
Abstract: Oral administration is a preferred model for studying infection by bacterial enteropathogens such as Yersinia spp. In the mouse model, the most frequent method for oral infection consists of oral gavage with a feeding needle directly introduced in the animal stomach via the esophagus. In this study, we compared needle gavage to bread feeding as an alternative mode of bacterial administration. Using bioluminescence-expressing strains of Yersinia pseudotuberculosis and Yersinia enterocolitica, we detected very early upon needle gavage a bioluminescent signal in the neck area together with a signal in the abdominal region, highlighting the presence of two independent sites of bacterial colonization and multiplication., Oral administration is a preferred model for studying infection by bacterial enteropathogens such as Yersinia spp. In the mouse model, the most frequent method for oral infection consists of oral gavage with a feeding needle directly introduced in the animal stomach via the esophagus. In this study, we compared needle gavage to bread feeding as an alternative mode of bacterial administration. Using bioluminescence-expressing strains of Yersinia pseudotuberculosis and Yersinia enterocolitica, we detected very early upon needle gavage a bioluminescent signal in the neck area together with a signal in the abdominal region, highlighting the presence of two independent sites of bacterial colonization and multiplication. Bacteria were often detected in the esophagus and trachea, as well as in the lymph nodes draining the salivary glands, suggesting that lesions made during needle introduction into the animal oral cavity lead to rapid bacterial draining to proximal lymph nodes. We then tested an alternative mode of bacterial administration using pieces of bread containing bacteria. Upon bread feeding infection, mice exhibited a stronger bioluminescent signal in the abdominal region than with needle gavage, and no signal was detected in the neck area. Moreover, Y. pseudotuberculosis incorporated in the bread is less susceptible to the acidic environment of the stomach and is therefore more efficient in causing intestinal infections. Based on our observations, bread feeding constitutes a natural and more efficient administration method which does not require specialized skills, is less traumatic for the animal, and results in diseases that more closely mimic foodborne intestinal infection.
Published: 2020

3. Intracellular offspring released from SFB filaments are flagellated

Author: Valérie Gaboriau-Routhiau, Vincent Jung, Jacomina Krijnse-Locker, Olivier Gorgette, Philippe J. Sansonetti, Céline Mulet, Nadine Cerf-Bensussan, Marion Bérard, Giulia Nigro, Ida Chiara Guerrera, Pamela Schnupf, Aurélie Couesnon, Yoshinori Umesaki, Maryse Moya-Nilges, Tatsuichiro Shima, Gyanendra P. Dubey, Audrey Salles, Iris Nkamba, Laboratory of Intestinal Immunity (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), UFR Sciences humaines et sociales [Sociétés et Humanités] - Université Paris Cité (UFR SHS UPCité ), Université Paris Cité (UPCité), Pathogénie microbienne moléculaire, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme BioImagerie Ultrastructurale – Ultrastructural BioImaging Platform (UTechS UBI), Institut Pasteur [Paris] (IP), BioImagerie Photonique – Photonic BioImaging (UTechS PBI), Plateforme Protéomique Necker [SFR Necker] (PPN - 3P5), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Yakult Central institute [Tokyo], Animalerie centrale (Plate-forme), Collège de France - Chaire Microbiologie et Maladies infectieuses, Collège de France (CdF (institution)), Laboratoire Interaction Hôte-Microbiote [Institut Necker Enfants Malades, Paris], Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), French National Research Agency (ANR)ANR-10-INSB-04ERC Advanced Grant DECRYPT Pasteur LabEx IBEID Doctoral fellowship ERC Advanced Grant IMMUNOBIOTA Bill and Melinda Gates Foundation Grand Challenge Grant OPP1141322Pasteur Institute Paris Descartes Université Institut National de la Santé et de la Recherche Médicale (Inserm), We are grateful to the members of the Center for Gnotobiology of the Institut Pasteur (T. Angélique, E. Maranghi, M. Jacob and M.G. Lopez Dieguez) for technical support with the gnotobiotic mice and also thank C. Schmitt and R. Tournebize for technical assistance. We thank the UTechS PBI and UBI (Center for Resources and Research in Technology, Institut Pasteur, Paris), the France-BioImaging infrastructure network supported by the ANR (ANR-10-INSB-04, Investments for the Future) and the Région Ile-de-France (programme DIM-Malinf) for the use of the Zeiss LSM 780 Elyra PS1 microscope., ANR-16-CE92-0008,membrane dynamics,Rupture et réparation membranaire : stratégies d'assemblage virale(2016), European Project: 339579,EC:FP7:ERC,ERC-2013-ADG,DECRYPT(2014), European Project: 339407,EC:FP7:ERC,ERC-2013-ADG,IMMUNOBIOTA(2014), Salles, Audrey, Decrypting signals in the crypt. - DECRYPT - - EC:FP7:ERC2014-04-01 - 2019-03-31 - 339579 - VALID, Host-microbiota interactions across the gut immune system:lessons from early onset inflammatory bowel diseases and from gnotobiotic mice - IMMUNOBIOTA - - EC:FP7:ERC2014-03-01 - 2019-02-28 - 339407 - VALID, Université Paris Cité - UFR Sciences humaines et sociales [Sociétés et Humanités] (UPCité UFR SHS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université de Paris - Faculté des Sciences humaines et sociales [Sociétés et Humanités] (UP Faculté SHS), Université de Paris (UP), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Chaire Microbiologie et Maladies infectieuses, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
Subjects: Microbiology (medical), Offspring, [SDV]Life Sciences [q-bio], Immunology, Biology, Bacterial physiology, Applied Microbiology and Biotechnology, Microbiology, Article, Cell Line, 03 medical and health sciences, Bacteria, Anaerobic, Mice, Immune system, Ileum, Bacterial development, Genetics, Animals, Humans, Intestinal Mucosa, 030304 developmental biology, 0303 health sciences, Segmented filamentous bacterium, 030306 microbiology, Cell Biology, Gene Expression Regulation, Bacterial, Bacterial host response, Cell biology, Rats, [SDV] Life Sciences [q-bio], Toll-Like Receptor 5, Flagella, Intracellular, Ileal epithelium, Flagellin
Abstract: International audience; The gut commensal segmented filamentous bacterium (SFB) attaches to the ileal epithelium and potently stimulates the host immune system. Using transmission electron microscopy (TEM), we show that mouse and rat SFB are flagellated above the concave tip at the unicellular intracellular offspring (IO) stage and that flagellation occurs prior to full IO differentiation and release of IOs from SFB filaments. This finding adds a missing link to the SFB life cycle.
Published: 2019

4. A Listeria monocytogenes Bacteriocin Can Target the Commensal Prevotella copri and Modulate Intestinal Infection

Author: Hannah Fehlner-Peach, Andrew T. Gewirtz, Massimo Marzorati, Marie-Anne Nahori, Benoit Chassaing, Alexandra Moura, Marion Bérard, Olivier Dussurget, Dan R. Littman, Nathalie Rolhion, Tom Van de Wiele, Pascale Cossart, Marc Lecuit, Jana De Bodt, DIAKITE, andrée, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, ERA-NET Infect-ERA - Subversive pro- and anti-inflammation trade-offs promote infection by Listeria monocytogenes - - PROANTILIS2013 - ANR-13-IFEC-0004 - IFEC - VALID, Bacterial, cellular and epigenetic factors that control enteropathogenicity - BacCellEpi - - H20202015-10-01 - 2018-09-30 - 670823 - VALID, Interactions Bactéries-Cellules (UIBC), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Georgia State University, University System of Georgia (USG), Universiteit Gent = Ghent University (UGENT), Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des Maladies infectieuses et tropicales [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Animalerie centrale (Plate-forme), Institut Pasteur [Paris] (IP), New York University School of Medicine, NYU System (NYU), Howard Hughes Medical Institute [New York] (HHMI), Howard Hughes Medical Institute (HHMI)-New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC), This work was supported by grants to P.C.: ERC Advanced Grant BacCellEpi (670823), ANR (Investissement d’Avenir Programme 10-LABX-62-IBEID), ERANET Infect-ERA PROANTILIS (13-IFEC-0004-02), and the Fondation le Roch., We thank the CDTA (Orléans) and the Institut Pasteur Animalerie Centrale staff, especially K. Sébastien, T. Angélique, M.G. Lopez Dieguez, M. Jacob, and E. Maranghi. We thank G. Jouvion and M. Tichit for technical help and the Centre Ressources Biologiques de l’Institut Pasteur for providing strains. We thank L. Maranghi, J. Blondou, and A. Lavelle for technical support and C. Bécavin, A. Hryckowian, B. Martinez, G. Eberl, G. Hansson, and H. Sokol for helpful discussion. N.R. was supported by an EMBO short-term fellowship (ASTF 399-2015), B.C. by a Career Development Award from the CCFA, an Innovator Award from the Kenneth Rainin Foundation, and a Seed Grant from the GSU’s Brain & Behavior program, H.F.-P. by an NYU-HCC CTSI grant (1TL1TR001447), and D.R.L. by the Howard Hughes Medical Institute and the Colton Center for Autoimmunity., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-13-IFEC-0004,PROANTILIS,Subversive pro- and anti-inflammation trade-offs promote infection by Listeria monocytogenes(2013), European Project: 670823,H2020,ERC-2014-ADG,BacCellEpi(2015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), Ghent University [Belgium] (UGENT), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP]-Institut des Maladies Génétiques Imagine [Paris], Institut des Maladies Génétiques Imagine [Paris], Institut Pasteur [Paris], Howard Hughes Medical Institute [New York], NYU System (NYU)-NYU System (NYU)-Columbia University Irving Medical Center (CUIMC)-Rockefeller University [New York], ANR-10-LABX-62-IBEID,IBEID,Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases'(2010), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Universiteit Gent = Ghent University [Belgium] (UGENT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Howard Hughes Medical Institute (HHMI)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC)-New York University School of Medicine, and NYU System (NYU)-NYU System (NYU)
Subjects: MUCUS, IMPACT, [SDV]Life Sciences [q-bio], medicine.disease_cause, M-SHIME, COLONIZATION, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MICROBIOTA, 3. Good health, [SDV] Life Sciences [q-bio], MUCOSAL, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Lmo2776, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, GROWTH, Prevotella copri, Bacteriocin, Virulence, Biology, Listeria infection, Microbiology, MATURATION, 03 medical and health sciences, Listeria monocytogenes, MUCINS, Virology, medicine, microbiota, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, 030304 developmental biology, Mucin, Biology and Life Sciences, biology.organism_classification, medicine.disease, Mucus, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, infection, Listeria, VIRULENCE, Parasitology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, RESISTANCE, 030217 neurology & neurosurgery, Bacteria, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Comment in The Strange Case of Prevotella copri: Dr. Jekyll or Mr. Hyde? [Cell Host Microbe. 2019]; International audience; Understanding the role of the microbiota components in either preventing or favoring enteric infections is critical. Here, we report the discovery of a Listeria bacteriocin, Lmo2776, which limits Listeria intestinal colonization. Oral infection of conventional mice with a Δlmo2776 mutant leads to a thinner intestinal mucus layer and higher Listeria loads both in the intestinal content and deeper tissues compared to WT Listeria. This latter difference is microbiota dependent, as it is not observed in germ-free mice. Strikingly, it is phenocopied by pre-colonization of germ-free mice before Listeria infection with Prevotella copri, an abundant gut-commensal bacteria, but not with the other commensals tested. We further show that Lmo2776 targets P. copri and reduces its abundance. Together, these data unveil a role for P.copri in exacerbating intestinal infection, highlighting that pathogens such as Listeria may selectively deplete microbiota bacterial species to avoid excessive inflammation.
Published: 2019

5. Excess calorie intake early in life increases susceptibility to colitis in adulthood

Author: Bernadette Polomack, Emelyne Lécuyer, Sophie Dulauroy, Marion Bérard, Pascal Campagne, Ziad Al Nabhani, Gérard Eberl, Microenvironnement et Immunité - Microenvironment and Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Animalerie centrale (Plate-forme), Institut Pasteur [Paris] (IP), We thank all the members of the Microenvironment & Immunity Unit, as well as from the Stroma, Inflammation & Tissue Repair Unit, for support and discussion. We also thank the members of Gnotobiology Platform of the Institut Pasteur for technical support with germfree mice. Z.A.N. was supported by Pasteur–Roux Postdoctoral Fellowships from the Institut Pasteur. This work was supported by Institut Pasteur and INSERM, the Association François Aupetit, the Fondation pour la Recherche Medicale, Janssen Horizon, and an Innovator award from the Kenneth Rainin Foundation, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]
Subjects: medicine.medical_specialty, Offspring, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Inflammatory bowel disease, 03 medical and health sciences, Mice, 0302 clinical medicine, Pregnancy, Physiology (medical), Internal medicine, Internal Medicine, medicine, Weaning, Animals, Homeostasis, Humans, Colitis, 030304 developmental biology, 2. Zero hunger, 0303 health sciences, Intestinal permeability, business.industry, Cell Biology, medicine.disease, Obesity, Ulcerative colitis, 3. Good health, Mice, Inbred C57BL, Endocrinology, Animals, Newborn, Maternal Exposure, 030220 oncology & carcinogenesis, Female, Disease Susceptibility, business, Energy Intake
Abstract: Epidemiological data reveal an association between obesity and inflammatory bowel disease (IBD). Furthermore, animal models demonstrate that maternal high-fat diet (HFD) and maternal obesity increase susceptibility to IBD in offspring. Here we report that excess calorie intake by neonatal mice, as a consequence of maternal HFD, forced feeding of neonates or low litter competition, leads to an increase during weaning in intestinal permeability, expression of pro-inflammatory cytokines and hydrogen sulfide production by the microbiota. These intestinal changes engage in mutual positive feedback that imprints increased susceptibility to colitis in adults. The pathological imprinting is prevented by the neutralization of IFN-γ and TNF-α or the production of hydrogen sulfide, or by normalization of intestinal permeability during weaning. We propose that excess calorie intake by neonates leads to multiple causally linked perturbations in the intestine that imprint the individual with long-term susceptibility to IBD. Al Nabhani et al. show how excessive caloric intake during the postnatal period increases the risk of developing intestinal bowel disease during adulthood, owing to increased intestinal permeability, cytokines and hydrogen sulfide production by the microbiota.
Published: 2018

6. A Weaning Reaction to Microbiota Is Required for Resistance to Immunopathologies in the Adult

Author: Marion Bérard, Tim Sparwasser, Rute Marques, Sophie Dulauroy, Clara Cousu, Shahed Al Bounny, Gérard Eberl, François Dejardin, Nadine Cerf-Bensussan, Ziad Al Nabhani, Microenvironnement et Immunité - Microenvironment and Immunity, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Johannes Gutenberg - Universität Mainz (JGU), Animalerie centrale (Plate-forme), Institut Pasteur [Paris], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Z.A.N. was supported by Pasteur-Roux Postdoctoral Fellowships from the Institut Pasteur. This work was supported by Institut Pasteur and INSERM, the Association François Aupetit, a Senior Research Award from the Crohn's and Colitis Foundation of America, the European Crohn’s and Colitis Organisation, the Fondation pour la Recherche Médicale, Janssen, and Innovator and Breakthrough awards from the Kenneth Rainin Foundation., We thank all the members of the Microenvironment & Immunity Unit, as well as those from the Stroma, Inflammation & Tissue Repair Unit, for support and discussion, the members of the Gnotobiology Platform of the Institut Pasteur for technical support with GF mice, the members of Biomics of the Institut Pasteur for microbial sequencing and analysis, and Ivo Gomperts Boneca (Institut Pasteur) for providing Myd88/Trif-double-deficient mice., Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Institut Pasteur [Paris] (IP), and CCSD, Accord Elsevier
Subjects: 0301 basic medicine, colitis, [SDV]Life Sciences [q-bio], short-chain fatty acids, Immunology, Retinoic acid, Tretinoin, Weaning, Biology, T-Lymphocytes, Regulatory, regulatory T cells, Allergic inflammation, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Immune system, RAR-related orphan receptor gamma, microbiota, medicine, Immunology and Allergy, Animals, inflammatory pathology, Colitis, Imprinting (psychology), Intestinal Mucosa, neonatal period, Nuclear Receptor Subfamily 1, Group F, Member 3, medicine.disease, Fatty Acids, Volatile, 3. Good health, Gastrointestinal Microbiome, [SDV] Life Sciences [q-bio], Mice, Inbred C57BL, 030104 developmental biology, Infectious Diseases, chemistry, Animals, Newborn, Solid food, 030220 oncology & carcinogenesis, mucosal immunity
Abstract: International audience; Microbes colonize all body surfaces at birth and participate in the development of the immune system. In newborn mammals, the intestinal microbiota is first shaped by the dietary and immunological components of milk and then changes upon the introduction of solid food during weaning. Here, we explored the reactivity of the mouse intestinal immune system during the first weeks after birth and into adulthood. At weaning, the intestinal microbiota induced a vigorous immune response—a “weaning reaction”—that was programmed in time. Inhibition of the weaning reaction led to pathological imprinting and increased susceptibility to colitis, allergic inflammation, and cancer later in life. Prevention of this pathological imprinting was associated with the generation of RORγt+ regulatory T cells, which required bacterial and dietary metabolites—short-chain fatty acids and retinoic acid. Thus, the weaning reaction to microbiota is required for immune ontogeny, the perturbation of which leads to increased susceptibility to immunopathologies later in life.
Published: 2018

7. Colorectal cancer specific conditions promote Streptococcus gallolyticus gut colonization

Author: Céline Mulet, Laetitia Aymeric, Philippe J. Sansonetti, Claire Poyart, Marion Bérard, Shaynoor Dramsi, Azadeh Saffarian, Béatrice Regnault, Patrick Trieu-Cuot, Laurence du Merle, Françoise Donnadieu, Giulia Nigro, Sylvie Robine, Pathogénie microbienne moléculaire, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie des Bactéries pathogènes à Gram-positif, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Animalerie centrale (Plate-forme), Institut Pasteur [Paris] (IP), Centre national de Référence des Streptocoques (CNR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Barrières et Pathogènes, [Institut Cochin] Departement Infection, immunité, inflammation, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut thématique multiorganismes Biologie Cellulaire, Développement et Evolution (ITMO BCDE), Alliance Nationale pour les Sciences de la vie et de la Santé [Paris] (AVIESAN), Génotypage des Eucaryotes (Plate-Forme), Collège de France - Chaire Microbiologie et Maladies infectieuses, Collège de France (CdF (institution)), This work was funded by La Ligue Nationale contre le Cancer, Association pour la Recherche sur le Cancer Foundation, the Research Applications and Industrial Partnerships Department of Pasteur Institute, the European Research Council (ERC), the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' Grant ANR-10-LABX-62-IBEID, ERC Grant DECRYPT 2013-ADG 339579 (to P.J.S.), and a gift from ONET Company. L.A. was supported by La Ligue Nationale contre le Cancer for 3 y and by ERC for 18 mo. P.J.S. is a Senior Foreign Scholar of the Howard Hughes Medical Institute., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 339579,EC:FP7:ERC,ERC-2013-ADG,DECRYPT(2014), Nigro, Giulia, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Decrypting signals in the crypt. - DECRYPT - - EC:FP7:ERC2014-04-01 - 2019-03-31 - 339579 - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], and Chaire Microbiologie et Maladies infectieuses
Subjects: 0301 basic medicine, MESH: Symporters, Colorectal cancer, medicine.drug_class, [SDV]Life Sciences [q-bio], colorectal cancer, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Bile Acids and Salts, Biology, Microbiology, 03 medical and health sciences, 0302 clinical medicine, S. bovis, MESH: Bacteriocins, Bacteriocin, bacteriocin, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Streptococcus gallolyticus, Colonization, MESH: Animals, MESH: Streptococcus gallolyticus, MESH: Mice, 2. Zero hunger, SLC10A2, MESH: Adenoma, MESH: Organic Anion Transporters, Sodium-Dependent, Multidisciplinary, MESH: Humans, Bile acid, Wnt signaling pathway, medicine.disease, MESH: Gene Expression Regulation, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, In vitro, digestive system diseases, [SDV] Life Sciences [q-bio], 030104 developmental biology, APC/Notch, 030220 oncology & carcinogenesis, biology.protein, MESH: Gastrointestinal Tract, S. gallolyticus, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Receptors, Notch, MESH: Colorectal Neoplasms
Abstract: Significance Growing evidence indicates a correlation between colorectal cancer and intestinal dysbiosis or colonization by single bacterial species such as Streptococcus gallolyticus subsp. gallolyticus (SGG), yet a causality link remains to be established. To address this point experimentally, we colonized Apc +/ − Notch-inducible mice with SGG. Apc +/ − is a pioneer somatic mutation driving the occurrence of polyps. We did not observe significant changes in the occurrence or development of polyps in this model. However, we observed a strong SGG colonization in Apc +/ − mice at the expense of resident enterococci. We related this ecological substitution to activation of a SGG-specific bacteriocin whose activity is induced in vivo by the detergent effect of an increased concentration of secondary bile acids in relation to oncogenic situation.
Published: 2018

8. A human immune system mouse model with robust lymph node development

Author: Hugo Mouquet, Grégory Jouvion, Helene Strick-Marchand, Ai Ing Lim, Nicolas Serafini, Zacarias Garcia, Philippe Bousso, Yan Li, Daniela Finke, Olivier Schwartz, Timothée Bruel, Ayrin Kök, Franck Bourgade, Guillemette Masse-Ranson, Thierry Hieu, Antoine Toubert, Mathilde Dusséaux, James P. Di Santo, Immunité Innée - Innate Immunity, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Dynamiques des Réponses immunes - Dynamics of Immune Responses, Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Réponse humorale aux pathogènes, Neuropathologie expérimentale / Experimental neuropathology, Institut Pasteur [Paris]-Université de Paris (UP), Animalerie centrale (Plate-forme), Institut Pasteur [Paris], Service d'Immunologie et d'Histocompatibilité, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Developmental Immunology, University of Basel (Unibas), This work was supported by the Agence Nationale de la Recherche (ANR) programme RPIB (Im_HIS to J.P.D.), the Laboratoire d’Excellence REVIVE (grant ANR-10-LABX-73 to Y.L. and J.P.D.), the Laboratoire d’Excellence Vaccine Research Institute (grant ANR-10-LABX-77 to T.B. and O.S.), the Laboratoire d’Excellence Milieu Intérieur (grant ANR-10-LABX-69 to H.M.), the Laboratoire d’Excellence IBEID (grant ANR-10-LABX-62 to O.S.), the Agence Nationale de Recherche sur le SIDA et les hepatitis (grant 15465 to O.S.), the European Commission Seventh Framework Programme no. 305578 (PathCO, to J.P.D.), the European Research Council (grant ERC-2013-StG 337146 to A.K. and T.H., grant ERC-2017-AvG 771167 to P.B.), Gilead Sciences (grant 00397 to G.M.-R. and J.P.D.), the Institut Pasteur (Core grant to J.P.D., G5 Program to H.M.), and INSERM (Core grant to J.P.D.)., ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010), ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 305578,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,PATHCO(2012), European Project: 337146,EC:FP7:ERC,ERC-2013-StG,HUMANTIVIRUSES(2014), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Vaccine Research Institute [Créteil, France] (VRI), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), and Institut Pasteur [Paris]-Université Paris Cité (UPCité)
Subjects: 0301 basic medicine, Male, T-Lymphocytes, MESH: Lymph Nodes, HIV Infections, Biochemistry, MESH: Mice, Knockout, MESH: HIV-1, Mice, MESH: Animals, Lymph node, Mice, Knockout, MESH: Cytokines, B-Lymphocytes, Mice, Inbred BALB C, MESH: Virus Latency, MESH: HIV Infections, 3. Good health, Virus Latency, medicine.anatomical_structure, Lymphatic system, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, MESH: Immunoglobulin Class Switching, Cytokines, Female, Lymph, Biotechnology, Interleukin Receptor Common gamma Subunit, MESH: Mice, Transgenic, Transgene, MESH: Mice, Inbred BALB C, Mice, Transgenic, Biology, MESH: Models, Immunological, 03 medical and health sciences, Immune system, Thymic Stromal Lymphopoietin, Immunity, MESH: Mice, Inbred C57BL, MESH: B-Lymphocytes, medicine, Animals, Humans, Secondary lymphoid tissue, Molecular Biology, MESH: Mice, MESH: Humans, MESH: Interleukin Receptor Common gamma Subunit, Models, Immunological, Cell Biology, Immunoglobulin Class Switching, MESH: Male, Mice, Inbred C57BL, 030104 developmental biology, MESH: T-Lymphocytes, Immunoglobulin class switching, Immunology, HIV-1, Lymph Nodes, MESH: Female
Abstract: International audience; Lymph nodes (LNs) facilitate the cellular interactions that orchestrate immune responses. Human immune system (HIS) mice are powerful tools for interrogation of human immunity but lack secondary lymphoid tissue (SLT) as a result of a deficiency in Il2rg-dependent lymphoid tissue inducer cells. To restore LN development, we induced expression of thymic-stromal-cell-derived lymphopoietin (TSLP) in a Balb/c Rag2-/-Il2rg-/-SirpaNOD (BRGS) HIS mouse model. The resulting BRGST HIS mice developed a full array of LNs with compartmentalized human B and T cells. Compared with BRGS HIS mice, BRGST HIS mice have a larger thymus, more mature B cells, and abundant IL-21-producing follicular helper T (TFH) cells, and show enhanced antigen-specific responses. Using BRGST HIS mice, we demonstrated that LN TFH cells are targets of acute HIV infection and represent a reservoir for latent HIV. In summary, BRGST HIS mice reflect the effects of SLT development on human immune responses and provide a model for visualization and interrogation of regulators of immunity.
Published: 2017

9. Lipopolysaccharide from crypt-specific core microbiota modulates the colonic epithelial proliferation-to-differentiation balance

Author: Tomoaki, Naito, Céline, Mulet, Cristina, De Castro, Antonio, Molinaro, Azadeh, Saffarian, Giulia, Nigro, Marion, Bérard, Mélanie, Clerc, Amy B, Pedersen, Philippe J, Sansonetti, Thierry, Pédron, Naito, Tomoaki, Mulet, Cã©line, De Castro, Cristina, Molinaro, Antonio, Saffarian, Azadeh, Nigro, Giulia, Bã©rard, Marion, Clerc, Mã©lanie, Pedersen, Amy B., Sansonetti, Philippe J., Pã©dron, Thierry, Lassailly-Bondaz, Anne, Pathogénie microbienne moléculaire, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Yakult Central institute [Tokyo], Dipartimento di Scienze Chimiche, University of Naples Federico II = Università degli studi di Napoli Federico II, Animalerie centrale (Plate-forme), Institut Pasteur [Paris] (IP), University of Edinburgh, Collège de France - Chaire Microbiologie et Maladies infectieuses, Collège de France (CdF (institution)), This work was supported by the European Research Council (advanced grant 339579to P.J.S.) and by grants from Danone Research and Yakult Research. A.B.P. was fundedby a Wellcome Trust CIIE Advanced Fellowship (095831) and University of EdinburghChancellors Fellowship, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Università degli studi di Napoli Federico II, Institut Pasteur [Paris], and Chaire Microbiologie et Maladies infectieuses
Subjects: Lipopolysaccharides, Necroptosi, LPS, Colon, necroptosis, Apoptosis, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, digestive system, Microbiology, Mice, Virology, Gram-Negative Bacteria, homeostasis, Homeostasi, Animals, Homeostasis, Intestinal Mucosa, intestinal stem cells, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Cells, Cultured, Cell Proliferation, Stem Cells, Microbiota, Intestinal stem cells, Cell Differentiation, Epithelial Cells, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, QR1-502, Gastrointestinal Microbiome, Necroptosis, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Intestinal stem cell, Research Article
Abstract: We identified a crypt-specific core microbiota (CSCM) dominated by strictly aerobic, nonfermentative bacteria in murine cecal and proximal colonic (PC) crypts and hypothesized that, among its possible functions, it may affect epithelial regeneration. In the present work, we isolated representative CSCM strains using selective media based upon our initial 16S rRNA-based molecular identification (i.e., Acinetobacter, Delftia, and Stenotrophomonas). Their tropism for the crypt was confirmed, and their influence on epithelial regeneration was demonstrated in vivo by monocolonization of germfree mice. We also showed that lipopolysaccharide (LPS), through its endotoxin activity, was the dominant bacterial agonist controlling proliferation. The relevant molecular mechanisms were analyzed using colonic crypt-derived organoids exposed to bacterial sonicates or highly purified LPS as agonists. We identified a Toll-like receptor 4 (TLR4)-dependent program affecting crypts at different stages of epithelial differentiation. LPS played a dual role: it repressed cell proliferation through RIPK3-mediated necroptosis of stem cells and cells of the transit-amplifying compartment and concurrently enhanced cell differentiation, particularly the goblet cell lineage., mBio, 8 (5), ISSN:2150-7511, ISSN:2161-2129
Published: 2017

10. Animal models are essential to biological research: issues and perspectives

Author: Xavier Montagutelli, Françoise Barré-Sinoussi, Régulation des Infections Rétrovirales, Institut Pasteur [Paris], Animalerie centrale (Plate-forme), The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties., and Institut Pasteur [Paris] (IP)
Subjects: human diseases, 0303 health sciences, Opinion, [SDV]Life Sciences [q-bio], Environmental ethics, Biology, animal models, animal welfare, 03 medical and health sciences, 0302 clinical medicine, animal protection, Animal welfare, preclinical studies, ComputingMilieux_MISCELLANEOUS, 030217 neurology & neurosurgery, animal research, 030304 developmental biology, Biotechnology
Abstract: International audience
Published: 2016

11. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota

Author: Elisabeth Chachaty, Alexander M.M. Eggermont, Vichnou Poirier-Colame, Jérôme Nigou, Antoine Roux, Gérard Eberl, Caroline Robert, Nicolas Jacquelot, Caroline Flament, Laurence Zitvogel, Franck Carbonnel, Silvia C. Formenti, Guido Kroemer, Didier Raoult, Paul Louis Woerther, Nadine Waldschmitt, David Enot, Marie Vétizou, Jonathan M. Pitt, Sonia Becharef, Romain Daillère, Christina Mateus, Sascha Cording, Paule Opolon, Sridhar Mani, Connie P.M. Duong, Nathalie Chaput, Bertrand Routy, Takahiro Yamazaki, Patricia Lepage, Ivo G. Boneca, Marion Bérard, Mathias Chamaillard, Florent Ginhoux, Sylvie Rusakiewicz, Maria Paula Roberti, Andreas Schlitzer, Encouse B. Golden, Université Paris-Sud - Paris 11 (UP11), Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sorbonne Paris Cité (USPC), New York University [New York] (NYU), NYU System (NYU), Microenvironnement et Immunité - Microenvironment and Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Albert Einstein College of Medicine [New York], Animalerie centrale (Plate-forme), Institut Pasteur [Paris] (IP), Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Pôle de biologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Université de la Méditerranée - Aix-Marseille 2, Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Hôpital Bicêtre, La Ligue contre le cancer, ARC, Ligue Nationale contre le Cancer (Equipes labelisees), Agence Nationale pour la Recherche (ANR AUTOPH), Agence Nationale pour la Recherche (ANR, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris], Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), ProdInra, Migration, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Adoptive cell transfer, Skin Neoplasms, medicine.medical_treatment, T-Lymphocytes, [SDV]Life Sciences [q-bio], B7-H1 Antigen, Mice, Cancer immunotherapy, Bacteroides, Innate, CTLA-4 Antigen, Melanoma, Cancer, Aged, 80 and over, Multidisciplinary, Host, Antibodies, Monoclonal, hemic and immune systems, Fecal Microbiota Transplantation, Middle Aged, 3. Good health, Anti-Bacterial Agents, [SDV] Life Sciences [q-bio], Intestines, medicine.anatomical_structure, Female, Immunotherapy, Adult, T cell, T-Cells, chemical and pharmacologic phenomena, Biology, Article, Polysaccharides, medicine, Germ-Free Life, Animals, Humans, Antibody, Aged, Molecule, medicine.disease, Ipilimumab, Blockade, Gastrointestinal Microbiome, Transplantation, Mice, Inbred C57BL, CTLA-4, Immunology, Dysbiosis, Bifidobacterium, Immunologic Memory, Model
Abstract: International audience; Antibodies targeting CTLA-4 have been successfully used as cancer immunotherapy. We find that the antitumor effects of CTLA-4 blockade depend on distinct Bacteroides species. In mice and patients, Tcell responses specific for B. thetaiotaomicron or B. fragilis were associated with the efficacy of CTLA-4 blockade. Tumors in antibiotic-treated or germ-free mice did not respond to CTLA blockade. This defect was overcome by gavage with B. fragilis, by immunization with B. fragilis polysaccharides, or by adoptive transfer of B. fragilis-specific T cells. Fecal microbial transplantation from humans to mice confirmed that treatment of melanoma patients with antibodies against CTLA-4 favored the outgrowth of B. fragilis with anticancer properties. This study reveals a key role for Bacteroidales in the immunostimulatory effects of CTLA-4 blockade.
Published: 2015

12. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide

Author: Christina Pfirschke, Charles O. Elson, Marion Bérard, Florent Ginhoux, Nadine Cerf-Bensussan, Mikael J. Pittet, Fabiana Saccheri, Lionel Apetoh, François Ghiringhelli, Eric Vivier, Elisabeth Chachaty, Guido Kroemer, Paul Louis Woerther, Paule Opolon, Andreas Schlitzer, Valérie Gaboriau-Routhiau, Sophie Viaud, Chantal Bizet, Bernhard Ryffel, Patricia Lepage, Gérard Eberl, Nadia Yessaad, David Enot, Camilla Engblom, Ivo G. Boneca, Grégoire Mignot, Chantal Ecobichon, Romain Daillère, Dalil Hannani, Dominique Clermont, Joël Doré, Laurence Zitvogel, Takahiro Yamazaki, Université Paris-Sud - Paris 11 (UP11), Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Apoptose, cancer et immunité (U848), Harvard Medical School [Boston] (HMS), Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Microbiologie, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Développement des Tissus Lymphoïdes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Animalerie centrale (Plate-forme), Institut Pasteur [Paris], Groupe Avenir, Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall (BGPB), Collection de l'Institut Pasteur (CIP), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, U989, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), IFR54 IRCIV, Institut de recherche intégrée en cancérologie, Laboratoire de Pathologie Expérimentale, Institut Gustave Roussy (IGR), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), University of Alabama at Birmingham [ Birmingham] (UAB), Apoptose, cancer et immunité (Equipe labellisée Ligue contre le cancer - CRC - Inserm U1138), Institut Gustave Roussy (IGR)-Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique - Hôpitaux de Paris, Université Paris Descartes - Paris 5 (UPD5), Groupe Avenir [Dijon], Programme ATIP - Avenir, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National du Cancer (INCa), la Ligue contre le cancer (LIGUE labelisee), SIRIC Socrates, LABEX, PACRI Onco-Immunology, European Research Council [202283], NIH [P01DK071176], ANR-11-PHUC-0002/11-PHUC-0002,PACRI,PACRI(2011), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-11-PHUC-0002,PACRI,Alliance Parisienne des Instituts de Recherche en Cancérologie(2011), ProdInra, Archive Ouverte, Pôle hospitalier Universitaire Cancer (PHUC) - Alliance Parisienne des Instituts de Recherche en Cancérologie - - PACRI2011 - ANR-11-PHUC-0002 - PHUC - VALID, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris-Sud - Paris 11 ( UP11 ), Immunologie des tumeurs et immunothérapie ( UMR 1015 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Apoptose, cancer et immunité ( U848 ), Harvard Medical School, Center for Systems Biology, Harvard University-Massachusetts General Hospital ( MGH ), Agency for Science, Technology and Research, Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale, Biologie et Génétique de la Paroi bactérienne, Collection de l'Institut Pasteur ( CIP ), MICrobiologie de l'ALImentation au Service de la Santé humaine ( MICALIS ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, Institut National de la Santé et de la Recherche Médicale-Université Paris Descartes - Paris 5 ( UPD5 ), Institut Gustave Roussy ( IGR ), Centre d'Immunologie de Marseille - Luminy ( CIML ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Immunologie et Neurogénétique Expérimentales et Moléculaires ( INEM ), Université d'Orléans ( UO ) -Centre National de la Recherche Scientifique ( CNRS ), The University of Alabama at Birmingham [ Birmingham] ( UAB ), Apoptose, cancer et immunité ( Equipe labellisée Ligue contre le cancer - CRC - Inserm U1138 ), Institut Gustave Roussy ( IGR ) -Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre d'Investigation Clinique en Biotherapie des cancers ( CIC 1428 , CBT 507 ), Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and ANR-11-PHUC-0002/11-PHUC-0002,PACRI,PACRI ( 2011 )
Subjects: Adoptive cell transfer, Cyclophosphamide, medicine.drug_class, Lymphoid Tissue, Gram-positive bacteria, [SDV]Life Sciences [q-bio], Antibiotics, Antineoplastic Agents, Gut flora, Gram-Positive Bacteria, Article, 03 medical and health sciences, Mice, 0302 clinical medicine, Immune system, Neoplasms, Intestine, Small, medicine, Tumor Microenvironment, Germ-Free Life, Animals, 030304 developmental biology, 0303 health sciences, Multidisciplinary, biology, [ SDV ] Life Sciences [q-bio], Microbiota, biology.organism_classification, Adoptive Transfer, Small intestine, 3. Good health, Anti-Bacterial Agents, Intestines, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Lymphatic system, 030220 oncology & carcinogenesis, Bacterial Translocation, Immunology, Cancer research, Th17 Cells, Immunologic Memory, Immunosuppressive Agents, medicine.drug
Abstract: The Microbiota Makes for Good Therapy The gut microbiota has been implicated in the development of some cancers, such as colorectal cancer, but—given the important role our intestinal habitants play in metabolism—they may also modulate the efficacy of certain cancer therapeutics. Iida et al. (p. 967 ) evaluated the impact of the microbiota on the efficacy of an immunotherapy [CpG (the cytosine, guanosine, phosphodiester link) oligonucleotides] and oxaliplatin, a platinum compound used as a chemotherapeutic. Both therapies were reduced in efficacy in tumor-bearing mice that lacked microbiota, with the microbiota important for activating the innate immune response against the tumors. Viaud et al. (p. 971 ) found a similar effect of the microbiota on tumor-bearing mice treated with cyclophosphamide, but in this case it appeared that the microbiota promoted an adaptive immune response against the tumors.
Published: 2013

13. Tissue tropism and target cells of NSs-deleted rift valley fever virus in live immunodeficient mice

Author: Michèle Bouloy, Nico van Rooijen, Grégory Jouvion, Céline Gommet, Tânia Zaverucha do Valle, Laurent Guillemot, Agnès Billecocq, Jean-Jacques Panthier, Xavier Montagutelli, Milena Hasan, Charlène Blanchet, Animalerie centrale (Plate-forme), Institut Pasteur [Paris] (IP), Génétique Moléculaire des Bunyavirus, Histopathologie humaine et Modèles animaux, Centre d'Immunologie Humaine (CIH), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique Fonctionnelle de la Souris, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Cytokines et Inflammation, Department of Molecular Cell Biology, VU Medical Center, Tânia Zaverucha do Valle was in receipt of fellowships from Conselho Nacional de Desenvolvimento Cientifico e Technological, Brazil (nu 210215/2006-2) and the Agence Nationale de la Recherche (ANR). This study was funded by the ANR grant ResistFever nu 07-GANI-007, the International Network for Capacity Building for the Control of Emerging Viral Vector Borne Zoonotic Diseases (Arbo-Zoonet) supported by the European Union under grant agreement nu 211757 and the Arbo-Zoonet Coordination Action Project nu211757 of the European Commission. The Mouse Functional Genetics Unit at the Institut Pasteur is funded by Merck Serono. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., ANR-07-GANI-0007,RESISTFEVER,Identification de gènes contrôlant la résistance à la Fièvre de la Vallée du Rift chez les mammifères domestiques(2007), European Project: 211757,EC:FP7:KBBE,FP7-KBBE-2007-1,ARBO-ZOONET(2008), PANTHIER, Jean-Jacques, Genanimal - Identification de gènes contrôlant la résistance à la Fièvre de la Vallée du Rift chez les mammifères domestiques - - RESISTFEVER2007 - ANR-07-GANI-0007 - GANI - VALID, International network for capacity building for the control of emerging viral vector borne zoonotic diseases - ARBO-ZOONET - - EC:FP7:KBBE2008-05-01 - 2012-10-31 - 211757 - VALID, Institut Pasteur [Paris], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Molecular cell biology and Immunology, and CCA - Immuno-pathogenesis
Subjects: Anatomy and Physiology, Rift Valley Fever, Veterinary Microbiology, Veterinary Anatomy and Physiology, [SDV.GEN] Life Sciences [q-bio]/Genetics, Viral Nonstructural Proteins, Gene Knockout Techniques, Mice, Macrophage, Mice, Knockout, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, Phagocytes, lcsh:Public aspects of medicine, Meningoencephalitis, Flow Cytometry, Immunohistochemistry, 3. Good health, medicine.anatomical_structure, Infectious Diseases, Veterinary Diseases, Liver, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Medicine, Veterinary Pathology, Research Article, Biotechnology, Veterinary Medicine, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, Animal Types, Immunology, Green Fluorescent Proteins, Spleen, Thymus Gland, Biology, Microbiology, Virus, 03 medical and health sciences, Model Organisms, medicine, Genetics, Animals, Pancreas, Vero Cells, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, 030306 microbiology, Monocyte, Public Health, Environmental and Occupational Health, lcsh:RA1-1270, medicine.disease, Rift Valley fever virus, Virology, Survival Analysis, Viral replication, Microscopy, Fluorescence, Liposomes, Vero cell, Tissue tropism, Veterinary Science, Clodronic Acid
Abstract: Background Rift Valley fever virus (RVFV) causes disease in livestock and humans. It can be transmitted by mosquitoes, inhalation or physical contact with the body fluids of infected animals. Severe clinical cases are characterized by acute hepatitis with hemorrhage, meningoencephalitis and/or retinitis. The dynamics of RVFV infection and the cell types infected in vivo are poorly understood. Methodology/Principal Findings RVFV strains expressing humanized Renilla luciferase (hRLuc) or green fluorescent protein (GFP) were generated and inoculated to susceptible Ifnar1-deficient mice. We investigated the tissue tropism in these mice and the nature of the target cells in vivo using whole-organ imaging and flow cytometry. After intraperitoneal inoculation, hRLuc signal was observed primarily in the thymus, spleen and liver. Macrophages infiltrating various tissues, in particular the adipose tissue surrounding the pancreas also expressed the virus. The liver rapidly turned into the major luminescent organ and the mice succumbed to severe hepatitis. The brain remained weakly luminescent throughout infection. FACS analysis in RVFV-GFP-infected mice showed that the macrophages, dendritic cells and granulocytes were main target cells for RVFV. The crucial role of cells of the monocyte/macrophage/dendritic lineage during RVFV infection was confirmed by the slower viral dissemination, decrease in RVFV titers in blood, and prolonged survival of macrophage- and dendritic cell-depleted mice following treatment with clodronate liposomes. Upon dermal and nasal inoculations, the viral dissemination was primarily observed in the lymph node draining the injected ear and in the lungs respectively, with a significant increase in survival time. Conclusions/Significance These findings reveal the high levels of phagocytic cells harboring RVFV during viral infection in Ifnar1-deficient mice. They demonstrate that bioluminescent and fluorescent viruses can shed new light into the pathogenesis of RVFV infection., Author Summary Rift Valley fever, caused by a member of the Bunyaviridae family, has spread during recent years to most sub-Saharan African countries, in Egypt and in the Arabian peninsula. The virus can be transmitted by insect vectors or by direct contacts with infectious tissues. The analysis of virus replication and dissemination in laboratory animals has been hampered by the need to euthanize sufficient numbers of animals and to assay appropriate organs at various time points after infection to evaluate the viral replication. By following the bioluminescence and fluorescence of Rift Valley fever viruses expressing light reporters, we were able to track the real-time dissemination of the viruses in live immunodeficient mice. We showed that the first infected organs were the thymus, spleen and liver, but the liver rapidly became the main location of viral replication. Phagocytes also appeared as important targets, and their systemic depletion by use of clodronate liposomes decreased the number of viruses in the blood, delayed the viral dissemination and prolonged the survival of the infected mice.
Published: 2011

14. Restricted Microbiota and Absence of Cognate TCR Antigen Leads to an Unbalanced Generation of Th17 Cells

Author: Tahia D. Fernandez, Johannes Snel, Gérard Eberl, Marion Bérard, Valérie Gaboriau-Routhiau, Matthias Lochner, Nadine Cerf-Bensussan, Philippe Bousso, Shinichiro Sawa, Siona Hauer, Développement des Tissus Lymphoïdes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institute of infection immunolog (TWINCORE), Centre for experimental and clinical infection research, Animalerie centrale (Plate-forme), Institut Pasteur [Paris], Institute of infection immunology (TWINCORE), Interactions de l'épithelium intestinal et du système immunitaire (UMR_S 793), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Recherche Agronomique (INRA), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Biologie des Populations Lymphocytaires, NIZO Food research, NIZO, Dynamiques des Réponses Immunes, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] - Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Recherche Agronomique (INRA), MICrobiologie de l'ALImentation au Service de la Santé humaine (MICALIS), Institut National de la Recherche Agronomique (INRA) - AgroParisTech, Institut Pasteur [Paris] - Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), NIZO [Ede, Netherlands], Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur, Maine de Paris, Agence Nationale de la Recherche, European Commission, Deutsche Forschungsgemeinschaft, Schlumberger Foundation, Hanover Medical School, and Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]
Subjects: Male, Segmented filamentous bacteria, ROR-GAMMA-T, Lymphocyte Activation, Mice, 0302 clinical medicine, INTESTINAL IMMUNE-RESPONSES, RAR-related orphan receptor gamma, RETINOIC ACID, Immunology and Allergy, ADAPTIVE IMMUNITY, Intestinal Mucosa, Orphan receptor, Mice, Knockout, 0303 health sciences, Interleukin-17, FOXP3, Cell Differentiation, Forkhead Transcription Factors, hemic and immune systems, T-Lymphocytes, Helper-Inducer, Nuclear Receptor Subfamily 1, Group F, Member 3, Cell biology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, [SDV.IMM] Life Sciences [q-bio]/Immunology, Intestinal lamina propria, Immunology, Green Fluorescent Proteins, Molecular Sequence Data, NKP46(+) CELLS, Receptors, Antigen, T-Cell, Mice, Transgenic, FILAMENTOUS BACTERIA, chemical and pharmacologic phenomena, Biology, 03 medical and health sciences, Antigen, Animals, Germ-Free Life, Amino Acid Sequence, REGULATORY T-CELLS, Gram-Positive Bacterial Infections, 030304 developmental biology, Cell Proliferation, T-cell receptor, LINEAGE COMMITMENT, CD4 Lymphocyte Count, HELPER-CELLS, PROINFLAMMATORY IL-17(+), 030215 immunology
Abstract: Retinoic acid-related orphan receptor (ROR)γt+ TCRαβ+ cells expressing IL-17, termed Th17 cells, are most abundant in the intestinal lamina propria. Symbiotic microbiota are required for the generation of Th17 cells, but the requirement for microbiota-derived Ag is not documented. In this study, we show that normal numbers of Th17 cells develop in the intestine of mice that express a single TCR in the absence of cognate Ag, whereas the microbiota remains essential for their development. However, such mice, or mice monocolonized with the Th17-inducing segmented filamentous bacteria, fail to induce normal numbers of Foxp3+ RORγt+ T cells, the regulatory counterpart of IL-17+RORγt+ T cells. These results demonstrate that a complex microbiota and cognate Ag are required to generate a properly regulated set of RORγt+ T cells and Th17 cells.
Published: 2011

15. Interleukin-7 treatment counteracts IFN-α therapy-induced lymphopenia and stimulates SIV-specific cytotoxic T lymphocyte responses in SIV-infected rhesus macaques

Author: Rémi Cheynier, Magali Rancez, Brigitte Assouline, Jacques Dutrieux, Céline Gommet, Iann Rance, Michel Morre, Annick Lim, Véronique Fabre-Mersseman, Sandra Rozlan, Stéphanie Beq, Brigitte Lemercier, Raphaelle Parker, Département de Virologie - Department of Virology, Institut Pasteur [Paris], Cythéris, Développement des Lymphocytes, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7), Animalerie centrale (Plate-forme), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by Institut Pasteur, Cytheris S.A., and the Agence Nationale de Recherches sur le SIDA et les hepatites virales. S.B. and V.F.-M. were the recipients of Agence Nationale de Recherches sur le SIDA et les hepatites virales postdoctoral grants., Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_treatment, T-Lymphocytes, [SDV]Life Sciences [q-bio], Immunology, Simian Acquired Immunodeficiency Syndrome, Lymphocyte Activation, Biochemistry, Antiviral Agents, 03 medical and health sciences, 0302 clinical medicine, Lymphopenia, medicine, Cytotoxic T cell, Animals, Humans, Interferon alfa, Immunodeficiency, 030304 developmental biology, 0303 health sciences, business.industry, Interleukin-7, Interleukin, Interferon-alpha, Cell Biology, Hematology, Immunotherapy, Viral Load, medicine.disease, Flow Cytometry, Virology, Macaca mulatta, 3. Good health, Cytokine, Simian Immunodeficiency Virus, Lymphocytopenia, business, Immunologic Memory, CD8, 030215 immunology, medicine.drug, T-Lymphocytes, Cytotoxic
Abstract: Interferon-α (IFN-α)–based therapy is presently the standard treatment for hepatitis C virus (HCV)–infected patients. Despite good effectiveness, this cytokine is associated with major side effects, including significant lymphopenia, that limits its use for HIV/HCV-coinfected patients. Interleukin-7 (IL-7) has recently shown therapeutic potential and safety in several clinical trials designed to demonstrate T-cell restoration in immunodeficient patients. The purpose of this study was to evaluate, in simian immunodeficiency virus-infected rhesus macaques, the relevance of IL-7 therapy as a means to overcoming IFN-α–induced lymphopenia. We showed that low-dose IFN-α treatment induced strong lymphopenia in chronically infected monkeys. In contrast, high-dose IFN-α treatment stimulated IL-7 production, leading to increased circulating T-cell counts. Moreover, IL-7 therapy more than abrogated the lymphopenic effect of low-dose IFN-α. Indeed, the association of both cytokines resulted in increased circulating T-cell counts, in particular in the naive compartments, as a consequence of central and peripheral homeostatic functions of the IL-7. Finally, reduced PD-1 expression by memory CD8+ T cells and transient T-cell repertoire diversification were observed under IL-7 therapy. Our data strongly suggest that IL-7 immunotherapy will be of substantial benefit in the treatment of HIV/HCV coinfection and should enhance the likelihood of HCV eradication in poorly responding patients.
Published: 2010

16. A New Mouse Model Reveals a Critical Role for Host Innate Immunity in Resistance to Rift Valley Fever

Author: do Valle, T. Z., Billecocq, A., Guillemot, L., Alberts, R., Gommet, C., Geffers, R., Calabrese, K., Schughart, K., Montagutelli, Xavier, Bouloy, M., Panthier, Jean-Jacques, Génétique Fonctionnelle de la Souris, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Génétique Moléculaire des Bunyavirus, Institut Pasteur [Paris] (IP), University of Veterinary Medicine Hannover (TiHo), Helmholtz Centre for Infection Research (HZI), Animalerie centrale (Plate-forme), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), This work was supported in part by 'ResistFever' Grant 07-GANI-007 from the Agence Nationale de la Recherche. It was also supported by a Programme Transversal de Recherche grant awarded to K.S., M.B., and J.-J.P. from the Helmholtz Centre for Infection Research and the Institut Pasteur. Part of this work was facilitated through the International Network for Capacity Building for the Control of Emerging Viral Vector Borne Zoonotic Diseases (Arbo-Zoonet) supported by the European Union under Grant Agreement 211757 and the Arbo-Zoonet Coordination Action Project 211757 of the European Commission. The Unité Fonctionnelle de la Souris at the Institut Pasteur is supported by Merck Serono. T.Z.V. was awarded fellowships from Conselho Nacional de Desenvolvimento Cientifico e Technologico, Brazil (210215/2006-2) and the Agence Nationale de la Recherche. R.A. is supported by the Helmholtz Virtual Centre 'GeNeSys–German Network for Systems Genetics.', ANR-07-GANI-0007,RESISTFEVER,Identification de gènes contrôlant la résistance à la Fièvre de la Vallée du Rift chez les mammifères domestiques(2007), European Project: 211757,EC:FP7:KBBE,FP7-KBBE-2007-1,ARBO-ZOONET(2008), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], and Fundação Oswaldo Cruz (FIOCRUZ)
Subjects: NSs, [SDV.GEN]Life Sciences [q-bio]/Genetics, Host genetics control, Rodent, Mouse, [SDV]Life Sciences [q-bio], embryonic structures, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Infectious diseases, Interferon, Viral
Abstract: International audience; Rift Valley fever (RVF) is an arthropod-borne viral disease repeatedly reported in many African countries and, more recently, in Saudi Arabia and Yemen. RVF virus (RVFV) primarily infects domesticated ruminants, resulting in miscarriage in pregnant females and death for newborns and young animals. It also has the ability to infect humans, causing a feverish syndrome, meningoencephalitis, or hemorrhagic fever. The various outcomes of RVFV infection in animals and humans argue for the existence of host genetic determinants controlling the disease. We investigated the susceptibility of inbred mouse strains to infection with the virulent RVFV ZH548 strain. Compared with classical BALB/cByJ mice, wild-derived Mus m. musculus MBT/Pas mice exhibited earlier and greater viremia and died sooner, a result in sharp contrast with their resistance to infection with West Nile virus and influenza A. Infection of mouse embryonic fibroblasts (MEFs) from MBT/Pas mice with RVFV also resulted in higher viral production. Microarray and quantitative RT-PCR experiments showed that BALB/cByJ MEFs displayed a significant activation of the type I IFN pathway. In contrast, MBT/Pas MEFs elicited a delayed and partial type I IFN response to RVFV infection. RNA interference-mediated inhibition of genes that were not induced by RVFV in MBT/Pas MEFs increased viral production in BALB/cByJ MEFs, thus demonstrating their functional importance in limiting viral replication. We conclude that the failure of MBT/Pas murine strain to induce, in due course, a complete innate immune response is instrumental in the selective susceptibility to RVF.
Published: 2010

17. Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis

Author: Christophe Brézillon, Djahida Bouskra, Ivo G. Boneca, Marion Bérard, Gérard Eberl, Catherine Werts, Rosa Varona, Développement des Tissus Lymphoïdes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Bactéries pathogènes entériques (BPE), Institut Pasteur [Paris], Animalerie centrale (Plate-forme), Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall (BGPB), Department of Immunology and Oncology, Universidad Autonoma de Madrid (UAM)-Centro Nacional de Biotecnologia, This work was supported by Institut Pasteur, CNRS, INSERM, ANR, Fondation de la Recherche Médicale, Mairie de Paris, a Marie Curie Excellence grant, La Fondation de France (D.B.) and la Ligue Nationale contre le Cancer (D.B.), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Universidad Autónoma de Madrid (UAM)-Centro Nacional de Biotecnología [Madrid] (CNB-CSIC), and Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)
Subjects: Male, Receptors, CCR6, Cell signaling, Gram-negative bacteria, beta-Defensins, Lymphoid Tissue, C-C chemokine receptor type 6, Peptidoglycan, Ligands, 03 medical and health sciences, Chemokine receptor, Mice, Peyer's Patches, 0302 clinical medicine, Immune system, Nod1 Signaling Adaptor Protein, NOD1, Gram-Negative Bacteria, Animals, Germ-Free Life, Homeostasis, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Chemokine CCL20, biology, Chimera, Innate lymphoid cell, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, biology.organism_classification, Cell biology, Immunoglobulin A, Intestines, Lymphatic system, Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Lymph Nodes, 030215 immunology
Abstract: Isolated lymphoid follicles (ILFs) are areas of specialized lymphoid tissue found in the lining of the small intestine where they are involved in protecting the host from invading pathogens. A new study of the composition of ILFs and the factors required for their formation has found that they are induced in the mouse small intestine by the presence of peptidoglycan from Gram-negative bacteria via recognition by the NOD1 innate receptor in epithelia cells. ILFs range from clusters of a few B cells to well-organized lymphoid nodules. Once established, the ILFs exert control over the make-up of the bacterial community. This rare example of microbe-induced tissue genesis in mammals demonstrates how a constructive 'dialogue' between bacteria and host can contribute to efficient digestion and protection from intestinal pathogens. The generation of isolated lymphoid follicles is shown to depend on NOD1-induced responses to bacterial components. Isolated lymphoid follicles are in turn are shown to affect the composition of the host microbiota. Intestinal homeostasis is critical for efficient energy extraction from food and protection from pathogens. Its disruption can lead to an array of severe illnesses with major impacts on public health, such as inflammatory bowel disease characterized by self-destructive intestinal immunity. However, the mechanisms regulating the equilibrium between the large bacterial flora and the immune system remain unclear. Intestinal lymphoid tissues generate flora-reactive IgA-producing B cells, and include Peyer's patches and mesenteric lymph nodes, as well as numerous isolated lymphoid follicles (ILFs)1,2. Here we show that peptidoglycan from Gram-negative bacteria is necessary and sufficient to induce the genesis of ILFs in mice through recognition by the NOD1 (nucleotide-binding oligomerization domain containing 1) innate receptor in epithelial cells, and β-defensin 3- and CCL20-mediated signalling through the chemokine receptor CCR6. Maturation of ILFs into large B-cell clusters requires subsequent detection of bacteria by toll-like receptors. In the absence of ILFs, the composition of the intestinal bacterial community is profoundly altered. Our results demonstrate that intestinal bacterial commensals and the immune system communicate through an innate detection system to generate adaptive lymphoid tissues and maintain intestinal homeostasis.
Published: 2008

18. Simple duplex fecal PCR assay that allows identification of false-negative results in Helicobacter sp.-infected mice

Author: Bourgade, F., Montagutelli, X., Bigbee, C., Weiss, A., Rigottier-Gois, L., Conti, C. J., Fernando Benavides, Animalerie centrale (Plate-forme), Institut Pasteur [Paris] (IP), Génétique des Mammifères, MD Anderson Cancer Center [Houston], The University of Texas Health Science Center at Houston (UTHealth), Unité de recherche d'Écologie et Physiologie du Système Digestif (UEPSD), Institut National de la Recherche Agronomique (INRA), This work was supported by NIH grants CA 09480, CA16672, and NIEHS grant ES007784., and Institut Pasteur [Paris]
Subjects: DNA, Bacterial, Quality Control, [SDV]Life Sciences [q-bio], MESH: Quality Control, MESH: Feces, Reproducibility of Results, MESH: Polymerase Chain Reaction, Mice, Inbred Strains, MESH: DNA, Bacterial, MESH: Mice, Inbred Strains, Polymerase Chain Reaction, MESH: Reproducibility of Results, Feces, Mice, MESH: Helicobacter, Laboratory Animal Science, MESH: Lactobacillus plantarum, Helicobacter, MESH: Laboratory Animal Science, Animals, MESH: Animals, MESH: Mice, False Negative Reactions, MESH: False Negative Reactions, Lactobacillus plantarum
Abstract: International audience; We designed a simple and sensitive duplex polymerase chain reaction (PCR) assay for detection of false-negative results during routine Helicobacter sp. feces analysis. We took advantage of the various Lactobacillus species that form part of the normal intestinal flora of laboratory rodents to improve our PCR diagnostic assays. Using this one-step PCR assay, we were able to rule out false-negative results without the need of adding internal standard molecules. This is an important quality control for PCR diagnostic tests, since the presence of inhibitors in feces can prevent detection of Helicobacter infections using PCR analysis. Use of this Lactobacillus group-specific PCR assay can be extended to other feces tests used in mouse quality-control programs.
Published: 2004

19. Lymphocytic choriomeningitis infection undetected by dirty-bedding sentinel monitoring and revealed after embryo transfer of an inbred strain derived from wild mice

Author: Ike, Fumio, Bourgade, Franck, Ohsawa, Kazutaka, Sato, Hiroshi, Morikawa, Shigeru, Saijo, Masayuki, Kurane, Ichiro, Takimoto, Kazuhiro, Yamada, Yasuko K., Jaubert, Jean, Berard, Marion, Nakata, Hatsumi, Hiraiwa, Noriko, Mekada, Kazuyuki, Takakura, Akira, Itoh, Toshio, Obata, Yuichi, Atsushi Yoshiki, Montagutelli, Xavier, RIKEN BioResource Research Center [Tsukuba, Japan] (RIKEN BRC), Animalerie centrale (Plate-forme), Institut Pasteur [Paris] (IP), Nagasaki University, National Institute of Infectious Diseases [Tokyo], Charles River Laboratories France [L'Arbresle], Central Institute for Experimental Animals [Kawasaki, Japan] (CIEA), FI is supported in part by the Strategic Programs for Research and Development (President’s Discretionary Fund) of RIKEN. RIKEN BRC collects and preserves mouse resources as a core facility of the National Bio-Resource Project in Japan and is supported by the Ministry of Education, Culture, Sports, Science, and Technology of Japan., and Institut Pasteur [Paris]
Subjects: MESH: Lymphocytic Choriomeningitis, viruses, [SDV]Life Sciences [q-bio], MESH: Vero Cells, Animals, Wild, Mice, Inbred Strains, chemical and pharmacologic phenomena, Lymphocytic Choriomeningitis, MESH: Mice, Inbred Strains, Rodent Diseases, Mice, MESH: Chlorocebus aethiops, Chlorocebus aethiops, Animals, Lymphocytic choriomeningitis virus, Serologic Tests, MESH: Animals, MESH: Animals, Wild, Animal Husbandry, Vero Cells, MESH: Mice, MESH: Animal Husbandry, MESH: Serologic Tests, virus diseases, MESH: Embryo Transfer, Embryo Transfer, MESH: Housing, Animal, Housing, Animal, MESH: Sentinel Surveillance, MESH: Lymphocytic choriomeningitis virus, MESH: Rodent Diseases, Sentinel Surveillance
Abstract: International audience; Persistent LCMV infection in wild-derived MAI/Pas mice housed under conventional conditions remained undetected for a decade, despite periodic health monitoring using dirty-bedding sentinels. When MAI/Pas mice were rederived by embryo transfer, recipient mothers produced antiLCMV antibodies, which first revealed the presence of the virus in the colony. Before this information was obtained, MAI/Pas mice had been shipped to another facility, undergone cesarean rederivation there, and been introduced into the recipient barrier. The foster mothers of rederived pups were LCMV-negative according to enzyme-linked immunosorbent assay, but sera of both cesarean-rederived MAI/Pas mice and their foster mothers were positive for LCMV infection by immunofluorescent assay (IFA). LCMV was isolated from the MAI/Pas mice, and its genomic RNA was sequenced. Examination of animal technicians in contact with LCMV-infected mice and of other mouse samples by IFA or a reverse transcriptase-polymerase chain reaction test (or both) revealed that neither the workers nor other animals had been infected with LCMV. Experimental data showed that LCMV transmission from persistently infected mice to naïve ones occurred only after direct contact of animals housed in the same cage. This experience demonstrates the importance of careful viral monitoring in the transfer of laboratory rodents between institutions, the limitation of dirty-bedding sentinels for detection of LCMV infection, and the inadequacy of cesarean rederivation for elimination of enzootic LCMV infection.

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19 results on '"Animalerie centrale (Plate-forme)"'

1. The Spatial Heterogeneity of the Gut Limits Predation and Fosters Coexistence of Bacteria and Bacteriophages

2. Bread Feeding Is a Robust and More Physiological Enteropathogen Administration Method Compared to Oral Gavage

3. Intracellular offspring released from SFB filaments are flagellated

4. A Listeria monocytogenes Bacteriocin Can Target the Commensal Prevotella copri and Modulate Intestinal Infection

5. Excess calorie intake early in life increases susceptibility to colitis in adulthood

6. A Weaning Reaction to Microbiota Is Required for Resistance to Immunopathologies in the Adult

7. Colorectal cancer specific conditions promote Streptococcus gallolyticus gut colonization

8. A human immune system mouse model with robust lymph node development

9. Lipopolysaccharide from crypt-specific core microbiota modulates the colonic epithelial proliferation-to-differentiation balance

10. Animal models are essential to biological research: issues and perspectives

11. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota

12. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide

13. Tissue tropism and target cells of NSs-deleted rift valley fever virus in live immunodeficient mice

14. Restricted Microbiota and Absence of Cognate TCR Antigen Leads to an Unbalanced Generation of Th17 Cells

15. Interleukin-7 treatment counteracts IFN-α therapy-induced lymphopenia and stimulates SIV-specific cytotoxic T lymphocyte responses in SIV-infected rhesus macaques

16. A New Mouse Model Reveals a Critical Role for Host Innate Immunity in Resistance to Rift Valley Fever

17. Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis

18. Simple duplex fecal PCR assay that allows identification of false-negative results in Helicobacter sp.-infected mice

19. Lymphocytic choriomeningitis infection undetected by dirty-bedding sentinel monitoring and revealed after embryo transfer of an inbred strain derived from wild mice

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