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20 results on '"Biomedical Primate Research Centre [Rijswijk] (BPRC)"'

1. Tolerant and intolerant macaques show different levels of contextual complexity in their vocal communication. Animal Behaviour

Author

Rebout, Nancy, Marco, Arianna De, Berg, Reinier van Den, Sanna, Andrea, Micheletta, Jérôme, Sterck, Elisabeth, Langermans, Jan, Lemasson, Alban, Thierry, Bernard, VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Fondazione Ethoikos, Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), University of Portsmouth, Utrecht University [Utrecht], Biomedical Primate Research Centre [Rijswijk] (BPRC), Ethologie animale et humaine (EthoS), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), and Alban Lemasson

Subjects
[SCCO]Cognitive science, [SCCO.NEUR]Cognitive science/Neuroscience, [SDV]Life Sciences [q-bio], [SDV.BA]Life Sciences [q-bio]/Animal biology, [SCCO.PSYC]Cognitive science/Psychology, [SDV.BDD]Life Sciences [q-bio]/Development Biology
Abstract

International audience

Published
2020

2. Robust continuous in vitro culture of the Plasmodium cynomolgi erythrocytic stages

Author

Kevin S. W. Tan, Kate Breyer, Georges Snounou, Clemens H. M. Kocken, Anne Elliot, Bruce Russell, Varakorn Kosaisavee, Bryan K. S. Yeung, Bee Huat Tan, Adeline C. Y. Chua, Rossarin Suwanarusk, Siti Nurdiana Abas, Rou Zhang, Anne-Marie Zeeman, Jee Sun Cho, Benoit Malleret, Laurent Rénia, Roger Le Grand, Dennis E. Kyle, Mary R. Galinski, Christophe Bodenreider, Nathalie Dereuddre-Bosquet, Chester J. Joyner, François Nosten, Dominique Mazier, Szczepan W Baran, Pablo Bifani, Amber Lange, Jessica Jie Ying Ong, Thierry T. Diagana, Steven P. Maher, Caitlin A. Cooper, Andy M. Yip, Institut des Maladies Emergentes et des Thérapies Innovantes (IMETI), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Global Health Division, Menzies School of Health Research, Mahidol Oxford Tropical Medicine Research Unit, University of Oxford [Oxford]-Mahidol University [Bangkok], Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biomedical Primate Research Centre [Rijswijk] (BPRC), Institut Cochin (UMR_S567 / UMR 8104), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Novartis Institute for Tropical Diseases (NITD), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Oxford-Mahidol University [Bangkok], and ANR-17-CE13-0025,IMHyp,Recherches sur l'Hypnozoïte du Paludisme(2017)

Subjects
0301 basic medicine, Erythrocytes, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Science, General Physics and Astronomy, 02 engineering and technology, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Malaria transmission, Plasmodium cynomolgi, Anopheles, parasitic diseases, in vitro culture, medicine, Parasite hosting, Model protists, Animals, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, lcsh:Science, Multidisciplinary, Drug discovery, Monkey Diseases, High-throughput screening, Plasmodium falciparum, General Chemistry, 021001 nanoscience & nanotechnology, biology.organism_classification, medicine.disease, Virology, In vitro, 3. Good health, Malaria, 030104 developmental biology, Macaca, lcsh:Q, 0210 nano-technology
Abstract

The ability to culture pathogenic organisms substantially enhances the quest for fundamental knowledge and the development of vaccines and drugs. Thus, the elaboration of a protocol for the in vitro cultivation of the erythrocytic stages of Plasmodium falciparum revolutionized research on this important parasite. However, for P. vivax, the most widely distributed and difficult to treat malaria parasite, a strict preference for reticulocytes thwarts efforts to maintain it in vitro. Cultivation of P. cynomolgi, a macaque-infecting species phylogenetically close to P. vivax, was briefly reported in the early 1980s, but not pursued further. Here, we define the conditions under which P. cynomolgi can be adapted to long term in vitro culture to yield parasites that share many of the morphological and phenotypic features of P. vivax. We further validate the potential of this culture system for high-throughput screening to prime and accelerate anti-P. vivax drug discovery efforts., Present understanding of Plasmodium vivax biology is hampered by its inability to grow in vitro. Here, the authors developed an in vitro culture of its simian counterpart, P. cynomolgi, which shares morphological and phenotypic similarities with P. vivax, initiating a new phase in vivax research.

Published
2019
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3. Anti-MOG autoantibodies pathogenicity in children and macaques demyelinating diseases

Author

Joanna Demilly, Julie Massonneau, Romain Marignier, Roger LeGrand, Jean Boutonnat, Philippe Hantraye, Bert A. 't Hart, Nicolas Tchitchek, Audrey Perrin, Julien Flament, Ché Serguera, Vanessa Contreras, Carole Leroy, Lev Stimmer, Claire-Maëlle Fovet, Pascale Chrétien, Philippe Horellou, Kumaran Deiva, Clovis Adam, Service MIRCEN (MIRCEN), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie François JACOB (JACOB), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL), Groupe Hospitalier Universitaire Paris-Sud (GHUPS), Biomedical Primate Research Centre [Rijswijk] (BPRC), University Medical Center Groningen [Groningen] (UMCG), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), CHU Grenoble, Hôpital Bicêtre, INSERM, CEA, ANRS (France Recherche Nord&Sud Sida-HIV Hépatites), Molecular Neuroscience and Ageing Research (MOLAR), Modélisation des biothérapies, Molecular Imaging Research Center, Fontenay aux Roses, Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Immunologie antivirale systémique et cérébrale, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de recherche Virologie et Immunologie Moléculaires (VIM), Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut d'Imagerie BioMédicale (I2BM), Pierre Wertheimer, Département de Neurologie, Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Service d'Anatomie Pathologique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Flament, Julien, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre

Subjects
Male, Neurology, Brain inflammation, [SDV]Life Sciences [q-bio], lcsh:RC346-429, 0302 clinical medicine, immune system diseases, Child, 0303 health sciences, biology, EAE, General Neuroscience, Experimental autoimmune encephalomyelitis, MULTIPLE-SCLEROSIS, Pathophysiology, 3. Good health, [SDV] Life Sciences [q-bio], EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS, Child, Preschool, Cytokines, Female, Antibody, Demyelination, medicine.medical_specialty, Encephalomyelitis, Autoimmune, Experimental, Adolescent, Immunology, MODELS, Complement, CSF, Myelin oligodendrocyte glycoprotein, 03 medical and health sciences, Cellular and Molecular Neuroscience, MYELIN OLIGODENDROCYTE GLYCOPROTEIN, medicine, Animals, Humans, lcsh:Neurology. Diseases of the nervous system, 030304 developmental biology, Autoantibodies, business.industry, Multiple sclerosis, Research, Autoantibody, Anti-MOG IgG, medicine.disease, Pathogenicity, nervous system diseases, nervous system, ANTIBODIES, biology.protein, Macaca, Myelin-Oligodendrocyte Glycoprotein, business, 030217 neurology & neurosurgery, Demyelinating Diseases
Abstract

Background Autoantibodies against myelin oligodendrocyte glycoprotein (anti-MOG-Abs) occur in a majority of children with acquired demyelinating syndromes (ADS) and physiopathology is still under investigation. As cynomolgus macaques immunized with rhMOG, all develop an experimental autoimmune encephalomyelitis (EAE), we assessed relatedness between anti-MOG-Abs associated diseases in both species. Methods The study includes 27 children followed for ADS and nine macaques with rhMOG-induced EAE. MRI lesions, cytokines in blood, and CSF at onset of ADS or EAE, as well as histopathological features of brain lesions were compared. Results Twelve children with anti-MOG-Abs ADS (ADS MOG+) and nine macaques with EAE, presented increased IL-6 and G-CSF in the CSF, whereas no such signature was found in 15 ADS MOG−. Furthermore, IgG and C1q were associated to myelin and phagocytic cells in brains with EAE (n = 8) and in biopsies of ADS MOG+ (n = 2) but not ADS MOG− children (n = 1). Macaque brains also revealed prephagocytic lesions with IgG and C1q depositions but no leukocyte infiltration. Conclusions Children with ADS MOG+ and macaques with EAE induced with rhMOG, present a similar cytokine signature in the CSF and a comparable aspect of brain lesions indicating analogous pathophysiological processes. In EAE, prephagocytic lesions points at IgG as an initial effector of myelin attack. These results support the pertinence of modeling ADS MOG+ in non-human primates to apprehend the natural development of anti-MOG-associated disease, find markers of evolution, and above all explore the efficacy of targeted therapies to test primate-restricted molecules.

Published
2019
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4. A quick and robust MHC typing method for free-ranging and captive primate species

Author

K. Stanbury, N. Poirier, N. G. de Groot, Ronald E. Bontrop, N.G. de Groot, G. Blancho, G.G.M. Doxiadis, A. J. M. de Vos-Rouweler, C. de Luna, Department of Comparative Genetics and Refinement [Rijswijk, The Netherlands], Biomedical Primate Research Centre [Rijswijk] (BPRC), Writtle College [Essex, UK], University of Essex, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Theoretical Biology and Bioinformatics [Utrecht, The Netherlands], Utrecht University [Utrecht], NIH/NIAID project HHSN272201100013C., and Le Bihan, Sylvie

Subjects
0301 basic medicine, Primates, Male, DNA Copy Number Variations, Genotype, Population, Immunology, Pre-clinical research, Major histocompatibility complex, Major Histocompatibility Complex, 03 medical and health sciences, Hylobates, Genetics, Animals, Humans, Typing, Copy-number variation, education, Microsatellites, Gene, Genotyping, Phylogeny, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Polymorphism, Genetic, biology, Conservation biology, biology.organism_classification, 030104 developmental biology, biology.protein, Microsatellite, Original Article, Female, MHC, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Microsatellite Repeats
Abstract

Gene products of the major histocompatibility complex (MHC) of human and non-human primates play a crucial role in adaptive immunity, and most of the relevant genes not only show a high degree of variability (polymorphism) but also copy number variation (CNV) is observed. Due to this diversity, MHC proteins influence the capability of individuals to cope with various pathogens. MHC and/or MHC-linked gene products such as odorant receptor genes are thought to influence mate choice and reproductive success. Therefore, MHC typing of wild and captive primate populations is considered to be useful in conservation biology, which is, however, often hampered by the need of invasive and time-consuming methods. All intact Mhc-DRB genes in primates appear to possess a complex and highly divergent microsatellite, DRB-STR. A panel of 154 pedigreed olive baboons (Papio anubis) was examined for their DRB content by DRB-STR analysis of genomic DNA. Using the same methodology on DNA of feces samples, DRB variability of a silvery gibbon population (Hylobates moloch) (N = 24), an endangered species, could successfully be studied. In both species, length determination of the DRB-STR resulted in the definition of unique genotyping patterns that appeared to be specific for a certain chromosome. Moreover, the different STR lengths were shown to segregate with the allelic variation of the respective gene. The results obtained expand data gained previously on DRB-STR typing in macaques, great apes, and humans and strengthen the conclusion that this protocol is applicable in molecular ecology, conservation biology, and colony management, especially of endangered primate species. Electronic supplementary material The online version of this article (doi:10.1007/s00251-016-0968-0) contains supplementary material, which is available to authorized users.

Published
2017

5. Intradermal vaccination prevents anti-MOG autoimmune encephalomyelitis in macaques

Author

Fovet, Claire-Maëlle, Stimmer, Lev, Contreras, Vanessa, Horellou, Philippe, Hubert, Audrey, Seddiki, Nabila, Chapon, Catherine, Tricot, Sabine, Leroy, Carole, Flament, Julien, Massonneau, Julie, Tchitchek, Nicolas, 't Hart, Bert, Zurawski, Sandra, Klucar, Peter, Hantraye, Philippe, Deiva, Kumaran, Zurawski, Gérard, Oh, Sangkon, Le Grand, Roger, Serguera, Ché, Service MIRCEN (MIRCEN), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Biomedical Primate Research Centre [Rijswijk] (BPRC), University of Groningen [Groningen], University Medical Center Groningen [Groningen] (UMCG), Baylor Institute for Immunology Research (BIIR), Mayo Clinic [Scottsdale], Mayo Clinic, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut de Biologie François JACOB (JACOB), Physiopathologie et immunothérapies dans l’infection VIH [Créteil] (Inserm U955 Équipe 16), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris-Est Créteil Val-de-Marne - Faculté de médecine (UPEC Médecine), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Vaccine Research Institute [Créteil, France] (VRI), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Laboratoire Archéomatériaux et Prévision de l'Altération (LAPA - UMR 3685), Nanosciences et Innovation pour les Matériaux, la Biomédecine et l'Energie (ex SIS2M) (NIMBE UMR 3685), Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), IRAMAT - Centre Ernest Babelon (IRAMAT-CEB), Institut de Recherches sur les Archéomatériaux (IRAMAT), Université de Technologie de Belfort-Montbeliard (UTBM)-Université d'Orléans (UO)-Université Bordeaux Montaigne (UBM)-Centre National de la Recherche Scientifique (CNRS)-Université de Technologie de Belfort-Montbeliard (UTBM)-Université d'Orléans (UO)-Université Bordeaux Montaigne (UBM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Hôpital Bicêtre, Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Research paper, Encephalomyelitis, Autoimmune, Experimental, Autoantigens, TGFβ, immune system diseases, Animals, Humans, Lymphocytes, Autoantibodies, Vaccines, EAE, Vaccination, hemic and immune systems, Dendritic Cells, Anti-MOG IgG, Recombinant Proteins, nervous system diseases, Treg, Phenotype, nervous system, Cytokines, Macaca, [SDV.IMM]Life Sciences [q-bio]/Immunology, Myelin-Oligodendrocyte Glycoprotein, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, Tolerance, Macaque
Abstract

International audience; BACKGROUND: Autoimmune demyelinating diseases (ADD) are a major cause of neurological disability due to autoreactive cellular and humoral immune responses against brain antigens. A cure for chronic ADD could be obtained by appropriate immunomodulation.METHODS: We implemented a preclinical scheme to foster immune tolerance to myelin oligodendrocyte glycoprotein (MOG), in a cynomolgus-macaque model of experimental autoimmune encephalomyelitis (EAE), in which administration of recombinant human MOG (rhMOG) elicits brain inflammation mediated by MOG-autoreactive CD4+ lymphocytes and anti-MOG IgG. For immunotherapy, we used a recombinant antibody (Ab) directed against the dendritic cell-asialoglycoprotein receptor (DC-ASGPR) fused either to MOG or a control antigen PSA (prostate-specific antigen).FINDINGS: rhMOG and the anti-DC-ASGPR-MOG were respectively detected in CD1a+ DCs or CD163+ cells in the skin of macaques. Intradermal administration of anti-DC-ASGPR-MOG, but not control anti-DC-ASGPR-PSA, was protective against EAE. The treatment prevented the CD4+ T cell activation and proinflammatory cytokine production observed in controls. Moreover, the administration of anti-DC-ASGPR-MOG induced MOG-specific CD4+CD25+FOXP3+CD39+ regulatory lymphocytes and favoured an upsurge in systemic TGFβ and IL-8 upon rhMOG re-administration in vivo.INTERPRETATION: We show that the delivery of an anti-DC-ASGPR-MOG allows antigen-specific adaptive immune modulation to prevent the breach of immune tolerance to MOG. Our findings pave the way for therapeutic vaccines for long-lasting remission to grave encephalomyelitis with identified autoantigens, such as ADD associated with anti-MOG autoantibodies. FUND: Work supported by the French ANR (ANR-11-INBS-0008 and ANR-10-EQPX-02-01), NIH (NIH 1 R01 AI 105066), the Baylor Scott and White Healthcare System funding and Roche Research Collaborative grants.

Published
2019
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6. The C-Type Lectin Receptor DC-SIGN Has an Anti-Inflammatory Role in Human M(IL-4) Macrophages in Response to Mycobacterium tuberculosis

Author

Geanncarlo Lugo-Villarino, Anthony Troegeler, Luciana Balboa, Claire Lastrucci, Carine Duval, Ingrid Mercier, Alan Bénard, Florence Capilla, Talal Al Saati, Renaud Poincloux, Ivanela Kondova, Frank A. W. Verreck, Céline Cougoule, Isabelle Maridonneau-Parini, Maria del Carmen Sasiain, Olivier Neyrolles, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anatomie et cytologie pathologiques [Purpan], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Compartimentation et dynamique cellulaires (CDC), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Biomedical Primate Research Centre [Rijswijk] (BPRC), and Immunometabolism and Macrophages in Tuberculosis/Human Immunodeficiency Virus-1 Co-infection (IM-TB/HIV)

Subjects
0301 basic medicine, lcsh:Immunologic diseases. Allergy, Chemokine, CD14, medicine.medical_treatment, Immunology, DC-SIGN, Microbiology, 03 medical and health sciences, C-type lectin, medicine, Immunology and Allergy, Macrophage, Interleukin 4, ComputingMilieux_MISCELLANEOUS, anti-inflammatory, biology, CLEC7A, Mycobacterium tuberculosis, 3. Good health, macrophages, 030104 developmental biology, Cytokine, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, C-type lectin receptors, lcsh:RC581-607
Abstract

DC-SIGN (CD209/CLEC4L) is a C-type lectin receptor (CLR) that serves as a reliable cell-surface marker of interleukin 4 (IL-4)-activated human macrophages [M(IL-4)], which historically represent the most studied subset within the M2 spectrum of macrophage activation. Although DC-SIGN plays important roles in Mycobacterium tuberculosis (Mtb) interactions with dendritic cells, its contribution to the Mtb-macrophage interaction remains poorly understood. Since high levels of IL-4 are correlated with tuberculosis (TB) susceptibility and progression, we investigated the role of DC-SIGN in M(IL-4) macrophages in the TB context. First, we demonstrate that DC-SIGN expression is present both in CD68+ macrophages found in tuberculous pulmonary lesions of non-human primates, and in the CD14+ cell population isolated from pleural effusions obtained from TB patients (TB-PE). Likewise, we show that DC-SIGN expression is accentuated in M(IL-4) macrophages derived from peripheral blood CD14+ monocytes isolated from TB patients, or in macrophages stimulated with acellular TB-PE, arguing for the pertinence of DC-SIGN-expressing macrophages in TB. Second, using a siRNA-mediated gene silencing approach, we performed a transcriptomic analysis of DC-SIGN-depleted M(IL-4) macrophages and revealed the upregulation of pro-inflammatory signals in response to challenge with Mtb, as compared to control cells. This pro-inflammatory gene signature was confirmed by RT-qPCR, cytokine/chemokine-based protein array, and ELISA analyses. We also found that inactivation of DC-SIGN renders M(IL-4) macrophages less permissive to Mtb intracellular growth compared to control cells, despite the equal level of bacteria uptake. Last, at the molecular level, we show that DC-SIGN interferes negatively with the pro-inflammatory response and control of Mtb intracellular growth mediated by another CLR, Dectin-1 (CLEC7A). Collectively, this study highlights a dual role for DC-SIGN as, on the one hand, being a host factor granting advantage for Mtb to parasitize macrophages and, on the other hand, representing a molecular switch to turn off the pro-inflammatory response in these cells to prevent potential immunopathology associated to TB.

Published
2018
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7. Selective Blockade of CD28-Mediated T Cell Costimulation Protects Rhesus Monkeys against Acute Fatal Experimental Autoimmune Encephalomyelitis

Author

Krista G, Haanstra, Karin, Dijkman, Noun, Bashir, Jan, Bauer, Caroline, Mary, Nicolas, Poirier, Paul, Baker, Claire L, Crossan, Linda, Scobie, Bert A, 't Hart, Bernard, Vanhove, Biomedical Primate Research Centre [Rijswijk] (BPRC), Center for Brain Research [Vienna, Austria], Medizinische Universität Wien = Medical University of Vienna, Effimune SAS [Nantes], Glasgow Caledonian University (GCU), Department of Neuroscience [Groningen, the Netherlands], University of Groningen [Groningen]-University Medical Center Groningen [Groningen] (UMCG), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), This work was supported by the European Union Seventh Framework Programme (FP7/2007-2013) under Grant Agreement 281493: Tolerance Restoration in Autoimmune Diseases by Selective Manipulation of the CD28 Costimulatory Pathway., European Project: 281493,EC:FP7:HEALTH,FP7-HEALTH-2011-single-stage,TRIAD(2012), Molecular Neuroscience and Ageing Research (MOLAR), Le Bihan, Sylvie, and Tolerance Restoration In Autoimmune Diseases by selective manipulation of the CD28 costimulatory pathway - TRIAD - - EC:FP7:HEALTH2012-01-01 - 2014-12-31 - 281493 - VALID

Subjects
Encephalomyelitis, Autoimmune, Experimental, Encephalomyelitis, T-Lymphocytes, Immunology, Biology, Lymphocyte Activation, Real-Time Polymerase Chain Reaction, Myelin oligodendrocyte glycoprotein, Immune system, CD28 Antigens, MYELIN OLIGODENDROCYTE GLYCOPROTEIN, medicine, Immunology and Allergy, Animals, Humans, ADULT PATIENTS, B cell, POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDER, B-Lymphocytes, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Experimental autoimmune encephalomyelitis, CENTRAL-NERVOUS-SYSTEM, CD28, COMMON MARMOSETS, MULTIPLE-SCLEROSIS, medicine.disease, biology.organism_classification, Macaca mulatta, Recombinant Proteins, 3. Good health, Virus Latency, RHEUMATOID-ARTHRITIS, medicine.anatomical_structure, ANTIBODY, Virus Diseases, B-CELLS, NONHUMAN PRIMATE MODELS, biology.protein, Lymphocryptovirus, Antibody, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Costimulatory and coinhibitory receptor–ligand pairs on T cells and APC control the immune response. We have investigated whether selective blockade of CD28–CD80/86 costimulatory interactions, which preserves the coinhibitory CTLA4–CD80/86 interactions and the function of regulatory T (Treg) cells, abrogates the induction of experimental autoimmune encephalomyelitis (EAE) in rhesus monkeys. EAE was induced by intracutaneous immunization with recombinant human myelin oligodendrocyte glycoprotein (rhMOG) in CFA on day 0. FR104 is a monovalent, PEGylated-humanized Fab′ Ab fragment against human CD28, cross-reactive with rhesus monkey CD28. FR104 or placebo was administered on days 0, 7, 14, and 21. FR104 levels remained high until the end of the study (day 42). Placebo-treated animals all developed clinical EAE between days 12 and 27. FR104-treated animals did not develop clinical EAE and were sacrificed at the end of the study resulting in a significantly prolonged survival. FR104 treatment diminished T and B cell responses against rhMOG, significantly reduced CNS inflammation and prevented demyelination. The inflammatory profile in the cerebrospinal fluid and brain material was also strongly reduced. Recrudescence of latent virus was investigated in blood, spleen, and brain. No differences between groups were observed for the β-herpesvirus CMV and the polyomaviruses SV40 and SA12. Cross-sectional measurement of lymphocryptovirus, the rhesus monkey EBV, demonstrated elevated levels in the blood of FR104-treated animals. Blocking rhesus monkey CD28 with FR104 mitigated autoreactive T and B cell activation and prevented CNS pathology in the rhMOG/CFA EAE model in rhesus monkeys.

Published
2015
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8. Antagonist Anti-CD28 Therapeutics for the Treatment of Autoimmune Disorders

Author

Gilles Blancho, Luiz Vicente Rizzo, Pedro H. Papotto, Kathryn J. Wood, Fadi Fakhouri, Fadi Issa, Bernard Vanhove, Jean-Paul Soulillou, Masaaki Zaitsu, Laetitia Laurent, Bert A. 't Hart, Nicolas Poirier, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), OSE Immunotherapeutics [Nantes], Biomedical Primate Research Centre [Rijswijk] (BPRC), Department Neuroscience [Groningen, The Netherlands], University of Groningen [Groningen]-University Medical Center Groningen [Groningen] (UMCG), Instituto de Medicina Molecular [Lisbon, Portugal] (Faculdade de Medicina), Universidade de Lisboa = University of Lisbon (ULISBOA), Hospital Israelita Albert Einstein [São Paulo, Brazil], Nuffield Department of Surgical Sciences [Oxford, UK], University of Oxford, Centre d'Investigation Clinique (CIC) Biotherapy, Degauque, Nicolas, Universidade de Lisboa (ULISBOA), and University of Oxford [Oxford]

Subjects
lcsh:Immunologic diseases. Allergy, 0301 basic medicine, DELAYED-TYPE HYPERSENSITIVITY, [SDV.IMM] Life Sciences [q-bio]/Immunology, MONOCLONAL-ANTIBODY, Immunology, SELECTIVE BLOCKADE, Inflammation, Review, PRECLINICAL EFFICACY, medicine.disease_cause, Autoimmunity, 03 medical and health sciences, T cell costimulation, antibodies, autoimmunity, N.P. are shareholders and employees of OSE Immunotherapeutics, a biotech company, developing CD28 antagonists. J.-P.S. is a shareholder of OSE Immunotherapeutics, 0302 clinical medicine, SKIN INFLAMMATION, Drug Discovery, medicine, Immunology and Allergy, REGULATORY T-CELLS, COSTIMULATION BLOCKADE, biology, Effector, T-cell receptor, CD28, NONHUMAN-PRIMATES, ALLOGRAFT SURVIVAL, medicine.disease, Transplantation, 030104 developmental biology, Rheumatoid arthritis, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, DOMAIN ANTIBODY ANTAGONIST, medicine.symptom, Antibody, lcsh:RC581-607, 030215 immunology
Abstract

International audience; The effector functions of T lymphocytes are responsible for most autoimmune disorders and act by directly damaging tissues or by indirectly promoting inflammation and antibody responses. Co-stimulatory and co-inhibitory T cell receptor molecules are the primary pharmacological targets that enable interference with immune-mediated diseases. Among these, selective CD28 antagonists have drawn special interest, since they tip the co-stimulation/co-inhibition balance towards efficiently inhibiting effector T cells while promoting suppression by pre-existing regulatory T-cells. After having demonstrated outstanding therapeutic efficacy in multiple models of autoimmunity, inflammation and transplantation, and safety in phase-I studies in humans, selective CD28 antagonists are currently in early clinical development for the treatment of systemic lupus erythematous and rheumatoid arthritis. Here, we review the available proof of concept studies for CD28 antagonists in autoimmunity, with a special focus on the mechanisms of action.

Published
2017
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9. Biochemical characterization of Plasmodium falciparum CTP:phosphoethanolamine cytidylyltransferase shows that only one of the two cytidylyltransferase domains is active

Author

Alicia Contet, Emilie Pihan, Rachel Cerdan, Marina Lavigne, Kai Wengelnik, Blandine Alberge, Dominique Douguet, Clemens H. M. Kocken, Henri Vial, Sweta Maheshwari, Dynamique des interactions membranaires normales et pathologiques (DIMNP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Biomedical Primate Research Centre [Rijswijk] (BPRC), Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Models, Molecular, Protein Conformation, Membrane lipids, Cytidylyltransferase, Plasmodium falciparum, Protozoan Proteins, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Biology, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, Mice, Biosynthesis, Animals, Humans, Molecular Biology, Cellular localization, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, chemistry.chemical_classification, Phosphatidylethanolamine, 0303 health sciences, Mice, Inbred BALB C, Binding Sites, Phosphatidylethanolamines, 030302 biochemistry & molecular biology, RNA Nucleotidyltransferases, Cell Biology, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, biology.organism_classification, 3. Good health, Amino acid, Protein Structure, Tertiary, Kinetics, Enzyme, chemistry, Female, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], [CHIM.CHEM]Chemical Sciences/Cheminformatics
Abstract

The intra-erythrocytic proliferation of the human malaria parasite Plasmodium falciparum requires massive synthesis of PE (phosphatidylethanolamine) that together with phosphatidylcholine constitute the bulk of the malaria membrane lipids. PE is mainly synthesized de novo by the CDP:ethanolamine-dependent Kennedy pathway. We previously showed that inhibition of PE biosynthesis led to parasite death. In the present study we characterized PfECT [P. falciparum CTP:phosphoethanolamine CT (cytidylyltransferase)], which we identified as the rate-limiting step of the PE metabolic pathway in the parasite. The cellular localization and expression of PfECT along the parasite life cycle were studied using polyclonal antibodies. Biochemical analyses showed that the enzyme activity follows Michaelis–Menten kinetics. PfECT is composed of two CT domains separated by a linker region. Activity assays on recombinant enzymes upon site-directed mutagenesis revealed that the N-terminal CT domain was the only catalytically active domain of PfECT. Concordantly, three-dimensional homology modelling of PfECT showed critical amino acid differences between the substrate-binding sites of the two CT domains. PfECT was predicted to fold as an intramolecular dimer suggesting that the inactive C-terminal domain is important for dimer stabilization. Given the absence of PE synthesis in red blood cells, PfECT represents a potential antimalarial target opening the way for a rational conception of bioactive compounds.

Published
2013
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10. A fine-scale chimpanzee genetic map from population sequencing

Author

Zamin Iqbal, Oliver Venn, Peter Humburg, Adam Auton, John Broxholme, Gil McVean, Adi Fledel-Alon, Cord Melton, Simon Myers, Molly Przeworski, Julian Maller, Ryan D. Hernandez, Rory Bowden, Ivy Aneas, Ellen M. Leffler, Teresa L Street, Aarti Venkat, Marcelo A. Nobrega, Gerton Lunter, Susanne P. Pfeifer, Laure Ségurel, Ronald E. Bontrop, Peter Donnelly, Max Planck Institute for Meteorology (MPI-M), Max-Planck-Gesellschaft, University of Chicago, University of Agriculture Faisalabad (UAF), Department of Comparative Genetics and Refinement [Rijswijk, The Netherlands], and Biomedical Primate Research Centre [Rijswijk] (BPRC)

Subjects
Male, Pan troglodytes, Population, Biology, Polymorphism, Single Nucleotide, Evolution, Molecular, 03 medical and health sciences, 0302 clinical medicine, Species Specificity, Genetic variation, Animals, Humans, education, Gene, ComputingMilieux_MISCELLANEOUS, PRDM9, 030304 developmental biology, Recombination, Genetic, Genetics, 0303 health sciences, education.field_of_study, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Multidisciplinary, Base Sequence, Haplotype, Chromosome Mapping, Genetic Variation, High-Throughput Nucleotide Sequencing, Chromosome, Histone-Lysine N-Methyltransferase, Sequence Analysis, DNA, Chromosomes, Mammalian, Haplotypes, CpG site, Chromosomes, Human, Pair 2, CpG Islands, Female, 030217 neurology & neurosurgery, Recombination
Abstract

Going Ape Over Genetic Maps Recombination is an important process in generating diversity and producing selectively advantageous genetic combinations. Thus, changes in recombination hotspots may influence speciation. To investigate the variation in recombination processes in humans and their closest existing relatives, Auton et al. (p. 193 , published online 15 March) prepared a fine-scale genetic map of the Western chimpanzee and compared it with that of humans. While rates of recombination are comparable between humans and chimpanzees, the locations and genetic motifs associated with recombination differ between the species.

Published
2016
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11. Keep children away from macaque monkeys!

Author

Jean-Michel Mansuy, C. Debuisson, E. Grouteau, Isabelle Claudet, C. Bréhin, Hester Buitendijk, Catherine Mengelle, Henk Niphuis, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie [Toulouse], CHU Toulouse [Toulouse], Biomedical Primate Research Centre [Rijswijk] (BPRC), Hôpital des Enfants, Embodiment, social ineQualities, lifecoUrse epidemiology, cancer and chronIc diseases, intervenTions, methodologY (Equipe 5 - EQUITY), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, and CLAUDET, ISABELLE

Subjects
Male, Pediatrics, medicine.medical_specialty, 040301 veterinary sciences, media_common.quotation_subject, Acyclovir, Simian, Macaque, 0403 veterinary science, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, 0302 clinical medicine, Herpes virus, biology.animal, Monkey bite, Medicine, Animals, Humans, 030212 general & internal medicine, Girl, Bites and Stings, Child, ComputingMilieux_MISCELLANEOUS, media_common, Travel, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, biology, business.industry, Amoxicillin, 04 agricultural and veterinary sciences, General Medicine, biology.organism_classification, 3. Good health, Rabies Vaccines, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Child, Preschool, Macaca, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, human activities
Abstract

To warn physicians and parents about the risk of macaque bites, we present two pediatric cases (a 4-year-old boy and a 10-year-old girl) of bites sustained while on holiday. The young boy developed febrile dermohypodermitis and was hospitalized for IV antibiotic treatment. He received an initial antirabies vaccine while still in the holiday destination. Except for local wound disinfection and antibiotic ointment, the girl did not receive any specific treatment while abroad. Both were negative for simian herpes PCR. When travelling in countries or cities with endemic simian herpes virus, parents should keep children away from monkeys. Travel agencies, pediatricians and family physicians should better inform families about the zoonotic risk.

Published
2016

12. Differential patterns of vocal similarity in tolerant and intolerant macaques

Author

Marco, Arianna De, Rebout, Nancy, Massiot, Elodie, Sanna, Andrea, Sterck, Elisabeth H.M., Langermans, Jan A.M., Cozzolino, Roberto, Thierry, Bernard, Lemasson, Alban, Sub Animal Ecology, LAS/3’R Centre ULS, Animal Ecology, Fondazione Ethoikos, Parco Faunistico di Piano dell'Abatino, Ethologie Cognitive et Sociale, Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Institut Français du Cheval et de l'Equitation [Saumur]-Institut National de la Recherche Agronomique (INRA), Department of Biology, Animal Ecology, Utrecht University [Utrecht], Biomedical Primate Research Centre [Rijswijk] (BPRC), Ethologie animale et humaine (EthoS), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Ethoikos, Radicondoli, Parco Faunistico di Piano dell'Abattino, Parco Faunistico, Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Animal Ecology, Animal Science Department, Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU)-Normandie Université (NU)-Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Sub Animal Ecology, and LAS/3’R Centre ULS

Subjects
0106 biological sciences, Social style, Vocal communication, [SDV]Life Sciences [q-bio], Behavioral neuroscience, 010603 evolutionary biology, 01 natural sciences, Behavioral Neuroscience, biology.animal, [SDV.BA.ZV]Life Sciences [q-bio]/Animal biology/Vertebrate Zoology, Kinship, Learning, 0501 psychology and cognitive sciences, Primate, 050102 behavioral science & comparative psychology, ComputingMilieux_MISCELLANEOUS, Dominance, Group membership, biology, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, [SCCO.NEUR]Cognitive science/Neuroscience, 05 social sciences, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Evolutionary biology, Animal Science and Zoology
Abstract

The investigation of vocal similarity between individuals has provided evidence of the flexibility of communication signals. This study evaluates the impact of group membership, affiliative bonds, kinship and dominance on acoustic similarity in two primate species with different social styles, intolerant rhesus macaques and tolerant Tonkean macaques. We focused on the fundamental frequencies of the contact calls emitted by adult females. Close kinship promoted vocal similarity between individuals in both species, and also group membership in Tonkean macaques, indicating the involvement of experiential and/or genetic factors. In rhesus macaques more similarities were observed between partners with strong or weak dominance asymmetry than between those with medium asymmetry, which again points to the role of experience. No evidence was found that dominance influences vocal similarity in Tonkean macaques. Our results provide additional evidence to the flexibility of vocal signals produced by macaques, and reveal that it is influenced by social style.

Published
2019
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13. Designing artificial merozoites for a potential blood stage malaria vaccine by surface display of multiple Plasmodium antigens on Yarrowia yeast cells

Author

Madzak, Catherine, Faber, Bart, Rodriguez Garcia, Roberto, Génie et Microbiologie des Procédés Alimentaires (GMPA), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Biomedical Primate Research Centre [Rijswijk] (BPRC), and AgroParisTech-Institut National de la Recherche Agronomique (INRA)

Subjects
[SDV]Life Sciences [q-bio], parasitic diseases
Abstract

Designing artificial merozoites for a potential blood stage malaria vaccine by surface display of multiple Plasmodium antigens on Yarrowia yeast cells. 8. European Recombinant Protein Production Meeting (RPP8)

Published
2015

14. Low levels of polymorphisms and no evidence for diversifying selection on the Plasmodium knowlesi Apical Membrane Antigen 1 gene

Author

Clemens H. M. Kocken, Frederick Saul, Khamisah Abdul Kadir, Roberto Rodriguez-Garcia, Graham A. Bentley, Edmond J. Remarque, Bart W. Faber, Balbir Singh, Brigitte Vulliez Le Normand, Department of Parasitology, Biomedical Primate Research Centre [Rijswijk] (BPRC), Malaria Research Centre, Immunologie structurale, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), European Commission EUROMALVAC2 (contract QLK2-CT- 2002-01197), The Centre National de la Recherche Scientifique, The Universiti Malaysia Sarawak (grant number 01(TD03)/1003/2013(01)), European Commission EMVDA grant LSHP-CT-2007-037506, E(M)VI, The European (Malaria) Vaccine Initiative, and Universiti of Sarawak: Grant E14054/F05/54/PKI/09/2012(01), European Project: 40221,EMVDA, European Project, and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
Molecular Sequence Data, Protozoan Proteins, malaria, lcsh:Medicine, Antigens, Protozoan, Balancing selection, plasmodium knowlesi, polymorphism, parasitic diseases, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Amino Acid Sequence, Selection, Genetic, Allele, Apical membrane antigen 1, lcsh:Science, Gene, Genetics, MESH: plasmodium knowlesi, Polymorphism, Genetic, Multidisciplinary, Sequence Homology, Amino Acid, biology, Malaria vaccine, Haplotype, lcsh:R, Membrane Proteins, Sequence Analysis, DNA, biology.organism_classification, medicine.disease, Virology, 3. Good health, MESH: malaria, MESH: polymorphism, Haplotypes, apical membrane antigen 1, Plasmodium knowlesi, Mutation, lcsh:Q, MESH: apical membrane antigen 1, Malaria, Research Article
Abstract

International audience; Infection with Plasmodium knowlesi, a zoonotic primate malaria, is a growing human health problem in Southeast Asia. P. knowlesi is being used in malaria vaccine studies, and a number of proteins are being considered as candidate malaria vaccine antigens, including the Apical Membrane Antigen 1 (AMA1). In order to determine genetic diversity of the ama1 gene and to identify epitopes of AMA1 under strongest immune selection, the ama1 gene of 52 P. knowlesi isolates derived from human infections was sequenced. Sequence analysis of isolates from two geographically isolated regions in Sarawak showed that polymorphism in the protein is low compared to that of AMA1 of the major human malaria parasites, P. falciparum and P. vivax. Although the number of haplotypes was 27, the frequency of mutations at the majority of the polymorphic positions was low, and only six positions had a variance frequency higher than 10%. Only two positions had more than one alternative amino acid. Interestingly, three of the high-frequency polymorphic sites correspond to invariant sites in PfAMA1 or PvAMA1. Statistically significant differences in the quantity of three of the six high frequency mutations were observed between the two regions. These analyses suggest that the pkama1 gene is not under balancing selection, as observed for pfama1 and pvama1, and that the PkAMA1 protein is not a primary target for protective humoral immune responses in their reservoir macaque hosts, unlike PfAMA1 and PvAMA1 in humans. The low level of polymorphism justifies the development of a single allele PkAMA1-based vaccine.

Published
2015
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15. Human Herpesvirus 7 with Roseoloviruses Closely Related to African Great Apes Are Naturally Infected Supplemental material

Author

Lavergne, Anne, Donato, Damien, Gessain, Antoine, Niphuis, Henk, Nerrienet, Eric, Verschoor, Ernst J, Lacoste, Vincent, Laboratoire des Interactions Virus-Hôtes [Cayenne, Guyane Française], Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Biomedical Primate Research Centre [Rijswijk] (BPRC), Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), This study benefited from European commission grant REGPOT-CT-2011-285837-STRonGer within the FP7 program, European Project: 285837,EC:FP7:REGPOT,FP7-REGPOT-2011-1,STRONGER(2011), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris]

Subjects
MESH: Sequence Analysis, DNA, MESH: Molecular Sequence Data, viruses, MESH: DNA, Viral/chemistry, MESH: Roseolovirus/isolation & purification, MESH: Polymerase Chain Reaction, MESH: Africa, MESH: Roseolovirus/classification, MESH: Primate Diseases/virology, MESH: Cluster Analysis, MESH: Roseolovirus Infections/virology, MESH: Blood/virology, MESH: Genotype, MESH: Viral Proteins/genetics, MESH: Hominidae, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Roseolovirus Infections/veterinary, MESH: DNA, Viral/genetics, MESH: Animals, MESH: Roseolovirus/genetics, MESH: Sequence Homology, MESH: Phylogeny
Abstract

International audience; Primates are naturally infected with herpesviruses. During the last 15 years, the search for homologues of human herpesvirusesin nonhuman primates allowed the identification of numerous viruses belonging to the different herpesvirus subfamilies andgenera. No simian homologue of human herpesvirus 7 (HHV7) has been reported to date. To investigate the putative existence ofHHV7-like viruses in African great apes, we applied the consensus-degenerate hybrid oligonucleotide primers (CODEHOP) program-mediated PCR strategy to blood DNA samples from the four common chimpanzee subspecies (Pan troglodytes verus, P. t.ellioti, P. t. troglodytes, and P. t. schweinfurthii), pygmy chimpanzees (Pan paniscus), as well as lowland gorillas (Gorilla gorillagorilla). This study led to the discovery of a novel roseolovirus close to HHV7 in each of these nonhuman primate species andsubspecies. Generation of the partial glycoprotein B (1,111-bp) and full-length DNA polymerase (3,036/3,042-bp) gene sequencesallowed the deciphering of their evolutionary relationships. Phylogenetic analyses revealed that HHV7 and its Africangreat ape homologues formed well-supported monophyletic lineages whose topological resemblance to the host phylogeny issuggestive of virus-host codivergence. Notably, the evolutionary branching points that separate HHV7 from African great apeherpesvirus 7 are remarkably congruent with the dates of divergence of their hosts. Our study shows that African great apes arehosts of human herpesvirus homologues, including HHV7 homologues, and that the latter, like other DNA viruses that establishpersistent infections, have cospeciated with their hosts.

Published
2014
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16. Multiple Instances of Ancient Balancing Selection Shared Between Humans and Chimpanzees

Author

Jeffrey D. Wall, Molly Przeworski, Peter Donnelly, Rory Bowden, Guy Sella, Laure Ségurel, Ellen M. Leffler, Ziyue Gao, Oliver Venn, Ronald E. Bontrop, Susanne P. Pfeifer, Gilean McVean, Adam Auton, State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Max Planck Institute for Meteorology (MPI-M), Max-Planck-Gesellschaft, University of Chicago, Department of Comparative Genetics and Refinement [Rijswijk, The Netherlands], Biomedical Primate Research Centre [Rijswijk] (BPRC), Laboratoire d'Anthropologie, and Université de Turin

Subjects
0106 biological sciences, Pan troglodytes, General Science & Technology, Molecular Sequence Data, Population, Single-nucleotide polymorphism, Biology, Balancing selection, Major histocompatibility complex, Polymorphism, Single Nucleotide, 010603 evolutionary biology, 01 natural sciences, Article, 03 medical and health sciences, Genetic, Clinical Research, Genetic variation, Genetics, Animals, Humans, Selection, Genetic, Polymorphism, education, Selection, Gene, Genetic Association Studies, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, education.field_of_study, Genome, Multidisciplinary, Natural selection, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Base Sequence, Genome, Human, Human Genome, Haplotype, Single Nucleotide, Pedigree, Haplotypes, Host-Pathogen Interactions, biology.protein, Human
Abstract

Instances in which natural selection maintains genetic variation in a population over millions of years are thought to be extremely rare. We conducted a genome-wide scan for long-lived balancing selection by looking for combinations of SNPs shared between humans and chimpanzees. In addition to the major histocompatibility complex (MHC), we identified 125 regions in which the same haplotypes are segregating in the two species, all but two of which are non-coding. In six cases, there is evidence for an ancestral polymorphism that persisted to the present in humans and chimpanzees. Regions with shared haplotypes are significantly enriched for membrane glycoproteins, and a similar trend is seen among shared coding polymorphisms. These findings indicate that ancient balancing selection has shaped human variation and point to genes involved in host-pathogen interactions as common targets.

Published
2013
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17. Identification of the five human species including by real-time polymerase chain reaction

Author

Oddoux, O., Debourgogne, A., Kantele, A., Kocken, C. H., Jokiranta, T. S., Vedy, S., Puyhardy, J. M., Machouart, M., Service de Parasitologie-Mycologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Relations Hôte-Environnement (RHEM), Université Henri Poincaré - Nancy 1 (UHP), Service de Biologie Clinique, Hôpital d'Instruction des Armées Legouest, Service de Santé des Armées-Service de Santé des Armées, Division of Infectious Diseases, Department of Medicine, Helsinki University Central Hospital, Haartman Institute [Helsinki], Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Department of Parasitology, and Biomedical Primate Research Centre [Rijswijk] (BPRC)

Subjects
Life Sciences
Abstract

International audience; Recently, has been recognised as the fifth species causing malaria in humans. Hundreds of human cases infected with this originally simian species have been described in Asian countries and increasing numbers are reported in Europe from travellers. The growing impact of tourism and economic development in South and Southeast Asia are expected to subsequently lead to a further increase in cases both among locals and among travellers. is easily misidentified in microscopy as or . We developed new primers for the rapid and specific detection of this species by low-cost real-time polymerase chain reaction (PCR) and added this method to an already existing panel of primers used for the molecular identification of the other four species in one reaction. Reference laboratories should now be able to identify undisputably and rapidly , as it is a potentially fatal pathogen.

Published
2010
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18. A novel homologue of Human herpesvirus 6 in chimpanzees

Author

Ernst J. Verschoor, Vincent Lacoste, Eric Nerrienet, Antoine Gessain, Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Biomedical Primate Research Centre [Rijswijk] (BPRC), Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), V. L. was the recipient of a fellowship from La Fondation pour la Recherche Medicale (FRM) and from the ‘Virus Cancer Prevention' association, We thank Philippe Mauclere, Guy Dubreuil and Marie-Claude Georges-Courbot for their great help in obtaining some of the blood samples studied and their continuing interest in this work., Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris]

Subjects
Human cytomegalovirus, MESH: Herpesvirus 6, Human/genetics, Genes, Viral, Pan troglodytes, DNA polymerase, MESH: Sequence Homology, Amino Acid, Herpesvirus 6, Human, viruses, Molecular Sequence Data, DNA-Directed DNA Polymerase, Simian, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, Virus, 03 medical and health sciences, Betaherpesvirinae, Virology, medicine, Animals, Humans, MESH: Animals, MESH: Receptors, Chemokine/genetics, Gene, 030304 developmental biology, Genetics, 0303 health sciences, MESH: Humans, MESH: Molecular Sequence Data, Sequence Homology, Amino Acid, biology, MESH: Trans-Activators/genetics, 030306 microbiology, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], virus diseases, MESH: Genes, Viral, medicine.disease, biology.organism_classification, 3. Good health, MESH: DNA-Directed DNA Polymerase/genetics, MESH: Pan troglodytes/virology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Trans-Activators, biology.protein, Receptors, Chemokine, Human herpesvirus 6, Roseolovirus
Abstract

Among the Betaherpesvirinae, human cytomegalovirus is the only virus to possess simian homologues. Indeed, intriguingly, no close simian homologue of the roseoloviruses Human herpesvirus 6 (HHV-6) and Human herpesvirus 7 (HHV-7), the other two human members of the Betaherpesvirinae, has been identified to date. Here, the first simian homologue of HHV-6 is described, which was identified in common chimpanzees and designated PanHV6. By using a degenerate consensus PCR method, three different gene fragments were amplified, corresponding to the DNA polymerase (U38), β-chemokine receptor (U12) and viral transactivator (U42) genes, with 94–96 % (nucleotide) and 95–97 % (amino acid) sequence identity to the corresponding genes of HHV-6B. Analysis of 77 predominantly wild-caught chimpanzees identified a unique PanHV6 strain in 21 animals, with no viral sequence variation between the different chimpanzee subspecies that were found to be infected. Characterization of this virus represents a great potential to gain a better understanding of the diseases associated with HHV-6.

Published
2005
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19. IMGT, the international ImMunoGeneTics database

Author

Giudicelli, V., Chaume, D., Bodmer, J., Muller, W., Busin, C., Marsh, S., Bontrop, R., Marc, L., Malik, A., Lefranc, M. P., Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Department of Physics and Astronomy [Christchurch] (DPA), University of Canterbury [Christchurch], Department of Comparative Genetics and Refinement [Rijswijk, The Netherlands], Biomedical Primate Research Centre [Rijswijk] (BPRC), Theoretical Biology and Bioinformatics [Utrecht, The Netherlands], Utrecht University [Utrecht], Institut de Génétique Moléculaire de Montpellier (IGMM), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)

Subjects
Models, Molecular, Databases, Factual, Molecular Sequence Data, Receptors, Antigen, T-Cell, Immunoglobulins, Information Storage and Retrieval, chemical and pharmacologic phenomena, Major Histocompatibility Complex, Computer Communication Networks, 03 medical and health sciences, 0302 clinical medicine, Terminology as Topic, Immunogenetics, Genetics, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, 030304 developmental biology, Internet, 0303 health sciences, Base Sequence, Genes, Immunoglobulin, Data Collection, Genetic Variation, 3. Good health, Genes, T-Cell Receptor, Genes, Vertebrates, France, Sequence Analysis, Research Article, 030215 immunology
Abstract

IMGT, the international ImMunoGeneTics database, is an integrated database specializing in immunoglobulins, T-cell receptors (TcR) and major histocompatibility complex (MHC) of all vertebrate species, initiated and co-ordinated by Marie-Paule Lefranc, CNRS, Montpellier II University, Montpellier, France (lefranc@ligm.crbm.cnrs-mop.fr). IMGT includes two databases: LIGM-DB (for immunoglobulins and TcR) and MHC/HLA-DB. IMGT comprises expertly annotated sequences and alignment tables. LIGM-DB contains more than 19 000 immunoglobulin and TcR sequences from 78 species. MHC/HLA-DB contains class I and class II human leukocyte antigen alignment tables. An IMGT tool, DNAPLOT, developed for immunoglobulins, TcR and MHC sequence alignments, is also available. IMGT works in close collaboration with the EMBL database. IMGT goals are to establish a common data access to all immunogenetics data, including sequences, oligonucleotide primers, gene maps and other genetic data of immunoglobulins, TcR and MHC molecules, and to provide a graphical user-friendly data access. IMGT will have important implications in medical research (repertoire in autoimmune diseases, AIDS, leukemias, lymphomas), therapeutical approaches (antibody engineering), genome diversity and genome evolution studies. IMGT can be accessed at http://imgt.cnusc.fr:8104 and http://www.ebi.ac.uk/IMGT

Published
1997
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20. C-type lectin receptor DCIR modulates immunity to tuberculosis by sustaining type I interferon signaling in dendritic cells

Author

Troegeler, Anthony, Mercier, Ingrid, Cougoule, Céline, Pietretti, Danilo, Colom, André, Duval, Carine, Vu Manh, Thien-Phong, Capilla, Florence, Poincloux, Renaud, Pingris, Karine, Nigou, Jérôme, Rademann, Jörg, Dalod, Marc, Verreck, Frank, Al Saati, Talal, Lugo-Villarino, Geanncarlo, Lepenies, Bernd, Hudrisier, Denis, Neyrolles, Olivier, Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona (UB), 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), Institut National de la Santé et de la Recherche Médicale (INSERM), Compartimentation et dynamique cellulaires (CDC), Centre National de la Recherche Scientifique (CNRS)-Institut Curie-Université Pierre et Marie Curie - Paris 6 (UPMC), Freie Universität Berlin, Biomedical Primate Research Centre [Rijswijk] (BPRC), Service d'anatomie et cytologie pathologiques [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Department of Biomolecular Systems [Potsdam], Max Planck Institute of Colloids and Interfaces, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Service Anatomie et cytologie pathologiques [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Toulouse III - Paul Sabatier (UPS), Immunometabolism and Macrophages in Tuberculosis/Human Immunodeficiency Virus-1 Co-infection (IM-TB/HIV), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), UPS CREFRE US006, Service d'Histopathologie, and Centre Hospitalier Universitaire de Purpan (CHU Purpan)

Subjects
Mice, Knockout, [SDV]Life Sciences [q-bio], chemical and pharmacologic phenomena, Dendritic Cells, Macaca mulatta, Mice, Inbred C57BL, STAT1 Transcription Factor, PNAS Plus, Interferon Type I, Animals, Tuberculosis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Lectins, C-Type, Phosphorylation, Signal Transduction
Abstract

International audience; Immune response against pathogens is a tightly regulated process that must ensure microbial control while preserving integrity of the infected organs. Tuberculosis (TB) is a paramount example of a chronic infection in which antimicrobial immunity is protective in the vast majority of infected individuals but can become detrimental if not finely tuned. Here, we report that C-type lectin dendritic cell (DC) immunoreceptor (DCIR), a key component in DC homeostasis, is required to modulate lung inflammation and bacterial burden in TB. DCIR is abundantly expressed in pulmonary lesions in Mycobacterium tuberculosis-infected nonhuman primates during both latent and active disease. In mice, we found that DCIR deficiency impairs STAT1-mediated type I IFN signaling in DCs, leading to increased production of IL-12 and increased differentiation of T lymphocytes toward Th1 during infection. As a consequence, DCIR-deficient mice control M. tuberculosis better than WT animals but also develop more inflammation characterized by an increased production of TNF and inducible NOS (iNOS) in the lungs. Altogether, our results reveal a pathway by which a C-type lectin modulates the equilibrium between infection-driven inflammation and pathogen's control through sustaining type I IFN signaling in DCs.

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