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9 results on '"MESH: Immune Tolerance"'

1. Trained immunity, tolerance, priming and differentiation: distinct immunological processes

Author

Boris Novakovic, Andreas Schlitzer, Giuseppe Matarese, Zahi A. Fayad, Willem J. M. Mulder, Henk Stunnenberg, Andrew R. DiNardo, Niels P. Riksen, Joachim L. Schultze, Christine Stabell Benn, Joseph C. Sun, Eva Kaufmann, Shabaana A. Khader, Michael H. Sieweke, Siroon Bekkering, Stephanie Fanucchi, Luis B. Barreiro, Maziar Divangahi, Mihai G. Netea, Reinout van Crevel, Jordi Ochando, Peter Aaby, Shruti Naik, Leo A. B. Joosten, Triantafyllos Chavakis, Musa M. Mhlanga, Eicke Latz, David L. Williams, Jos W. M. van der Meer, Luke A. J. O'Neill, Ramnik J. Xavier, Nigel Curtis, Robert W. Sauerwein, Kate L. Jeffrey, Edward R. Sherwood, Elaine Fuchs, Sebastian Weis, Nargis Khan, Melanie Hamon, Raphael Duivenwoorden, Keiko Ozato, Simone J.C.F.M. Moorlag, Jorge Domínguez-Andrés, Frank L. van de Veerdonk, Precision Medicine, ICMS Core, McGill University Health Center [Montreal] (MUHC), Bandim Health Project, International Network for the Demographic Evaluation of Populations and Their Health (INDEPTH Network), Washington University in Saint Louis (WUSTL), The University of Chicago Medicine [Chicago], Radboud University Medical Center [Nijmegen], Technische Universität Dresden = Dresden University of Technology (TU Dresden), University of Melbourne, Baylor College of Medicine (BCM), Baylor University, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Eindhoven University of Technology [Eindhoven] (TU/e), University of Cape Town, Rockefeller University [New York], Chromatine et Infection - Chromatin and Infection, Institut Pasteur [Paris] (IP), Harvard Medical School [Boston] (HMS), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Institute of Experimental Endocrinology and Oncology (IEOS), National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), Trinity Biomedical Sciences Institute, School of Biochemistry & Immunology, National Institute of Child Health and Human Development [Bethesda], National Institutes of Health, Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Universität Bonn = University of Bonn, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biotechnology Center, and Center for Regenerative Therapies Dresden (CRTD), Max Delbrück Centrum für Molekulare Medizin (MDC), University of Southern Denmark (SDU), Radboud University [Nijmegen], Memorial Sloane Kettering Cancer Center [New York], Weill Medical College of Cornell University [New York], Jena University Hospital [Jena], East Tennessee State University (ETSU), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Massachusetts Institute of Technology (MIT), Divangahi, M., Aaby, P., Khader, S. A., Barreiro, L. B., Bekkering, S., Chavakis, T., van Crevel, R., Curtis, N., Dinardo, A. R., Dominguez-Andres, J., Duivenwoorden, R., Fanucchi, S., Fayad, Z., Fuchs, E., Hamon, M., Jeffrey, K. L., Khan, N., Joosten, L. A. B., Kaufmann, E., Latz, E., Matarese, G., van der Meer, J. W. M., Mhlanga, M., Moorlag, S. J. C. F. M., Mulder, W. J. M., Naik, S., Novakovic, B., O'Neill, L., Ochando, J., Ozato, K., Riksen, N. P., Sauerwein, R., Sherwood, E. R., Schlitzer, A., Schultze, J. L., Sieweke, M. H., Benn, C. S., Stunnenberg, H., Sun, J., van de Veerdonk, F. L., Weis, S., Williams, D. L., Xavier, R., Netea, M. G., Institut Pasteur [Paris], Consiglio Nazionale delle Ricerche (CNR), University of Bonn, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtzgemeinschaft, Radboud university [Nijmegen], Hamon, Melanie, and ACS - Atherosclerosis & ischemic syndromes

Subjects
0301 basic medicine, [SDV]Life Sciences [q-bio], animal diseases, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Priming (immunology), Adaptive Immunity, 0302 clinical medicine, Immunology and Allergy, MESH: Animals, ComputingMilieux_MISCELLANEOUS, immunology [BCG Vaccine], Vaccination, Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16], Cell Differentiation, Common framework, [SDV] Life Sciences [q-bio], MESH: BCG Vaccine, BCG Vaccine, MESH: Immunologic Memory, MESH: Immunity, Innate, MESH: Cell Differentiation, MESH: Immune Tolerance, Immunology, education, immunology [Adaptive Immunity], chemical and pharmacologic phenomena, Biology, Article, 03 medical and health sciences, Immune system, Immunity, Immune Tolerance, Animals, Humans, ddc:610, Molecular Biology, MESH: Humans, immunology [Immune Tolerance], Cell Biology, MESH: Vaccination, biochemical phenomena, metabolism, and nutrition, Immunity, Innate, immunology [Immunologic Memory], immunology [Immunity, Innate], Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], 030104 developmental biology, bacteria, Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19], Neuroscience, Immunologic Memory, MESH: Adaptive Immunity, 030215 immunology
Abstract

The similarities and differences between trained immunity and other immune processes are the subject of intense interrogation. Therefore, a consensus on the definition of trained immunity in both in vitro and in vivo settings, as well as in experimental models and human subjects, is necessary for advancing this field of research. Here we aim to establish a common framework that describes the experimental standards for defining trained immunity.

Published
2021

2. PD-1 is expressed by and regulates human group 3 innate lymphoid cells in human decidua

Author

Emanuela Marcenaro, Marco Greppi, Enrico Munari, Paola Vacca, Maria Cristina Mingari, Alessandro Moretta, Silvia Pesce, Lorenzo Moretta, Ezio Fulcheri, Daniel Olive, Department of Experimental Medicine - DIMES [Genoa, Italy] (DIMES), University of Genoa (UNIGE), Department of Experimental Medicine, University of Genoa, D.I.C.M.I., Universita degli studi di Genova, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Istituto Nazionale per la Ricerca sul Cancro, Genova, Immunologia, Università di Genova, Dipartimento di Medicina Sperimentale, IRCCS Istituto Giannina Gaslini, Genova, and Università degli studi di Genova = University of Genoa (UniGe)

Subjects
MESH: Signal Transduction, 0301 basic medicine, MESH: Trophoblasts, [SDV]Life Sciences [q-bio], Programmed Cell Death 1 Receptor, B7-H1 Antigen, MESH: Decidua, Immune tolerance, MESH: Pregnancy, 0302 clinical medicine, Pregnancy, MESH: B7-H1 Antigen, Homeostasis, Innate, Immunology and Allergy, Lymphocytes, Receptor, Hepatitis A Virus Cellular Receptor 2, MESH: Cytokines, Innate lymphoid cell, Decidua, MESH: Programmed Cell Death 1 Receptor, Trophoblasts, MESH: Placental Circulation, 3. Good health, Cell biology, medicine.anatomical_structure, MESH: Homeostasis, Cytokines, Female, MESH: Immunity, Innate, Signal transduction, Signal Transduction, Programmed cell death, MESH: Immune Tolerance, T cell, Immunology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, 03 medical and health sciences, Immune system, Immune Tolerance, medicine, Humans, Placental Circulation, MESH: Humans, Immunity, Immunity, Innate, MESH: Hepatitis A Virus Cellular Receptor 2, 030104 developmental biology, MESH: Lymphocytes, MESH: Female, 030215 immunology
Abstract

International audience; Group 3 innate lymphoid cells (ILC3) have been detected in both murine and human decidual tissues where they are thought to play a relevant role in the induction and maintenance of pregnancy. However, limited information exists on the molecular mechanisms that regulate these cells, including immune checkpoints. Here, we show that ILC3 express the inhibitory checkpoints programmed cell death (PD-1) and T cell immunoglobulin and mucin domain containing protein 3 (TIM-3) during the first trimester of pregnancy and that these receptors could regulate production of cytokines, including IL-22, IL-8, and TNF-α, induced by IL-23. We also show that the intermediate extravillous trophoblast (iEVT) expresses high levels of the PD-1-ligand PD-L1, suggesting that PD-1/PD-L1 interaction may regulate ILC3 function at the feto-maternal interface. Our present data provide the first evidence that human decidual ILC3 express a functional PD-1. It is possible that an altered expression or function of PD-1 may break the immune-tolerance resulting in pregnancy failure.

Published
2019

3. Tumor immunosurveillance and immunotherapies: a fresh look from intravital imaging

Author

Morgane Boulch, Capucine L. Grandjean, Philippe Bousso, Marine Cazaux, Dynamiques des Réponses immunes - Dynamics of Immune Responses, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), École normale supérieure de Lyon (ENS de Lyon), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), The work was supported by Institut Pasteur, Inserm, and an Advanced grant (ENLIGHTEN) from the European Research Council (P.B.)., We thank Mikael Pittet, Thorsten Mempel, and Thomas Gebhardt for kindly providing images., European Project: 741167,ERC-2016-ADG,ENLIGHTEN(2018), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], and École normale supérieure - Lyon (ENS Lyon)

Subjects
0301 basic medicine, Intravital Microscopy, Computer science, MESH: Immunotherapy, medicine.medical_treatment, immunosurveillance, 0302 clinical medicine, Cell Movement, Neoplasms, MESH: Tumor Microenvironment, Tumor Microenvironment, Immunology and Allergy, MESH: Monitoring, Immunologic, MESH: Animals, MESH: Neoplasms, Immunologic Surveillance, MESH: Cell Movement, Cell migration, Intravital Imaging, 3. Good health, Immunosurveillance, MESH: Tumor Escape, [SDV.IMM]Life Sciences [q-bio]/Immunology, immunotherapy, MESH: Immune Tolerance, Immunology, Tumor immunity, 03 medical and health sciences, MESH: Intravital Microscopy, Immune system, Monitoring, Immunologic, Immune Tolerance, medicine, Animals, Humans, two-photon microscopy, MESH: Immunologic Surveillance, Tumor microenvironment, two- photon microscopy, MESH: Humans, Tumor immunosurveillance, Immunotherapy, tumor immunity, Disease Models, Animal, 030104 developmental biology, Tumor Escape, intravital imaging, MESH: Disease Models, Animal, Neuroscience, 030215 immunology
Abstract

International audience; Understanding complex interactions between the immune system and the tumor microenvironment is an essential step towards the rational development and optimization of immunotherapies. Several experimental approaches are available to tackle this complexity but most are not designed to address the dynamic features of immune reactions, including cell migration, cellular interactions, and transient signaling events. By providing a unique means to access these precious parameters, intravital imaging offers a fresh look at intratumoral immune responses at the single-cell level. Here, we discuss how in vivo imaging sheds light on fundamental aspects of tumor immunity and helps elucidate modes of action of immunotherapies. We conclude by discussing future developments that may consolidate the unique contribution of intravital imaging for our understanding of tumor immunity.

Published
2019

4. Shigella -mediated immunosuppression in the human gut: subversion extends from innate to adaptive immune responses

Author

Philippe J. Sansonetti, Fatoumata Samassa, Armelle Phalipon, Katja Brunner, Pathogénie microbienne moléculaire, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Collège de France - Chaire Microbiologie et Maladies infectieuses, Collège de France (CdF (institution)), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Chaire Microbiologie et Maladies infectieuses, and Phalipon, Armelle

Subjects
medicine.medical_treatment, bacterial mucosal, mucosal, Review, MESH: Virulence, medicine.disease_cause, immunomodulation, MESH: Shigella, Type three secretion system, 0302 clinical medicine, Immunology and Allergy, Shigella, MESH: Animals, MESH: Immunity, Humoral, enteropathogen, 0303 health sciences, Immunosuppression, Acquired immune system, 3. Good health, MESH: Immunity, Innate, MESH: Intestines, type three secretion system, MESH: Immune Tolerance, MESH: Dysentery, Bacillary, infectious disease, Immunology, Adaptive immunity, T cells, Virulence, immune modulators, Biology, Microbiology, 03 medical and health sciences, dysentery, MESH: Type III Secretion Systems, Immune system, Human gut, parasitic diseases, medicine, bacterial, MESH: Mice, 030304 developmental biology, Pharmacology, MESH: Humans, MESH: Host-Pathogen Interactions, biochemical phenomena, metabolism, and nutrition, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, virulence, Infectious disease (medical specialty), bacteria, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Adaptive Immunity, 030215 immunology
Abstract

International audience; The enteropathogen, Shigella, is highly virulent and remarkably adjusted to the intestinal environment of its almost exclusive human host. Key for Shigella pathogenicity is the injection of virulence effectors into the host cell via its type three secretion system (T3SS), initiating disease onset and progression by the vast diversity of the secreted T3SS effectors and their respective cellular targets. The multifaceted modulation of host signaling pathways exerted by Shigella T3SS effectors, which include the subversion of host innate immune defenses and the promotion of intracellular bacterial survival and dissemination, have been extensively reviewed in the recent past. This review focuses on the human species specificity of Shigella by discussing some possible evasion mechanisms towards the human, but not non-human or rodent gut innate defense barrier, leading to the lack of a relevant animal infection model. In addition, subversion mechanisms of the adaptive immune response are highlighted summarizing research advances of the recent years. In particular, the new paradigm of Shigella pathogenicity constituted of invasion-independent T3SS effector-mediated targeting of activated, human lymphocytes is discussed. Along with consequences on vaccine development, these findings offer new directions for future research endeavors towards a better understanding of immunity to Shigella infection.

Published
2018

5. Liver macrophages: Friend or foe during hepatitis B infection?

Author

Julie Lucifora, Suzanne Faure-Dupuy, David Durantel, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lucifora, Julie, and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Hepatitis B virus, MESH: Immune Tolerance, Kupffer Cells, medicine.disease_cause, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Pathogenesis, 03 medical and health sciences, Immune system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Parenchyma, Immune Tolerance, Medicine, Humans, innate immunity inhibition, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Hepatitis, tolerance, MESH: Humans, MESH: Hepatitis B, Hepatology, business.industry, Macrophages, MESH: Host-Pathogen Interactions, MESH: Macrophages, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Hepatitis B, Phenotype, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Immunity, Innate, 3. Good health, Hepatitis B infection, MESH: Hepatitis B virus, MESH: Kupffer Cells, 030104 developmental biology, Liver, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Immunology, Host-Pathogen Interactions, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Hepatic stellate cell, MESH: Immunity, Innate, business, MESH: Liver
Abstract

International audience; The Hepatitis B virus chronically infects the liver of 250 million people worldwide. Over the past decades, major advances have been made in the understanding of Hepatitis B virus life cycle in hepatocytes. Beside these parenchymal cells, the liver also contains resident and infiltrating myeloid cells involved in immune responses to pathogens and much less is known about their interplay with Hepatitis B virus. In this review, we summarized and discussed the current knowledge of the role of liver macrophages (including Kupffer cells and liver monocyte-derived macrophages), in HBV infection. While it is still unclear if liver macrophages play a role in the establishment and persistence of HBV infection, several studies disclosed data suggesting that HBV would favour liver macrophage anti-inflammatory phenotypes and thereby increase liver tolerance. In addition, alternatively activated liver macrophages might also play in the long term a key role in hepatitis B-associated pathogenesis, especially through the activation of hepatic stellate cells. Therapies aiming at a transient activation of pro-inflammatory liver macrophages should therefore be considered for the treatment of chronic HBV infection.

Published
2018

6. Early expansion of circulating granulocytic myeloid-derived suppressor cells predicts development of nosocomial infections in septic patients

Author

Uhel, Fabrice, Azzaoui, Imane, Grégoire, Murielle, Pangault, Céline, Dulong, Joelle, Tadié, Jean-Marc, Gacouin, Arnaud, Camus, Christophe, Cynober, Luc, Fest, Thierry, Le Tulzo, Yves, Roussel, Mikael, Tarte, Karin, Service des Maladies Infectieuses et Réanimation Médicale, Hôpital Pontchaillou, Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Microenvironment, Cell Differentiation, Immunology and Cancer ( MICMAC ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Etablissement français du sang [Rennes] ( EFS Bretagne ), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d’immunologie, de thérapie cellulaire et d’hématopoïèse, Prévention et traitement de la perte protéique musculaire en situation de résistance à l'anabolisme ( PRETRRAM - EA 4466 ), Université Paris Descartes - Paris 5 ( UPD5 ), Service de biochimie et de génétique moléculaire [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Research grant from the French Intensive Care Society / Société de Réanimation de Langue Française (FICS/SRLF), Research grant from the National Institute of Cancer and Direction Générale de l'Organisation des Soins Ministère de la Santé (Projet Recherche Translationnelle 2010), Research grant from the Comité de la Recherche Translationnelle (CORECT), Rennes University Hospital, UHEL, Fabrice, Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Etablissement français du sang [Rennes] (EFS Bretagne), Prévention et traitement de la perte protéique musculaire en situation de résistance à l'anabolisme (PRETRRAM - EA 4466), Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
immune tolerance, MESH : monocytes, [SDV.IMM] Life Sciences [q-bio]/Immunology, MDSC, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, infections nosocomiales, choc septique, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], sepsis, MESH: immune tolerance, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], nosocomial infections, polynucléaires neutrophiles, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : granulocytes, MESH: granulocytes, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, MESH: Sepsis, [ SDV.IMM.II ] Life Sciences [q-bio]/Immunology/Innate immunity, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH: monocytes, cytométrie en flux, flow cytometry, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, granulocytes, myeloid-derived suppressor cells, cross infection, MESH: cross infection, MESH : immune tolerance, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.IMM]Life Sciences [q-bio]/Immunology, septic shock, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH : Sepsis, MESH : cross infection, monocytes, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Rationale - Sepsis induces a sustained immune dysfunction responsible for poor outcome and nosocomial infections. Myeloid-derived suppressor cells (MDSCs) described in cancer and inflammatory processes may be involved in sepsis-induced immune suppression, but their clinical impact remains poorly defined.Objectives - To clarify phenotype, suppressive activity, origin, and clinical impact of MDSCs in patients with sepsis.Methods - Peripheral blood transcriptomic analysis was performed on 29 patients with sepsis and 15 healthy donors. A second cohort of 94 consecutive patients with sepsis, 11 severity-matched intensive care patients, and 67 healthy donors was prospectively enrolled for flow cytometry and functional experiments.Measurements and main results - Genes involved in MDSC suppressive functions, including S100A12, S100A9, MMP8, and ARG1, were up-regulated in the peripheral blood of patients with sepsis. CD14HLA-DR monocytic (M)-MDSCs were expanded in intensive care unit patients with and without sepsis and CD14CD15 low-density granulocytes/granulocytic (G)-MDSCs were more specifically expanded in patients with sepsis (P Conclusions - M-MDSCs and G-MDSCs strongly contribute to T-cell dysfunction in patients with sepsis. More specifically, G-MDSCs producing arginase 1 are associated with a higher incidence of nosocomial infections and seem to be major actors of sepsis-induced immune suppression.

Published
2017

7. Inherent and Tumor-Driven Immune Tolerance in the Prostate Microenvironment Impairs Natural Killer Cell Antitumor Activity

Author

S. Brunelle, Mélanie Bentobji, Alessandro Moretta, Samuel Granjeaud, Gwenaelle Gravis, Flora Poizat, N. Salem, Palma Rocchi, Daniel Olive, Mathilde Guerin, Jeanne Thomassin-Piana, Francine Azario-Cheillan, Jochen Walz, Christine Pasero, Maria Paciencia-Gros, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), University of Genova [Genova, Italy], Rocchi, Palma, and Università degli studi di Genova = University of Genoa (UniGe)

Subjects
0301 basic medicine, Cytotoxicity, Immunologic, Male, MESH: Killer Cells, Natural, Cancer Research, MESH: Cell Line, Tumor, MESH: Immune Tolerance, Oncology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Biology, Immune tolerance, Natural killer cell, 03 medical and health sciences, Interleukin 21, Prostate cancer, 0302 clinical medicine, Cell Line, Tumor, MESH: Tumor Microenvironment, medicine, Immune Tolerance, Tumor Microenvironment, Humans, Prospective Studies, MESH: Cytotoxicity, Immunologic, Neoplasm Metastasis, Tumor microenvironment, MESH: Cytokines, Lymphokine-activated killer cell, MESH: Humans, Prostatic Neoplasms, Immunotherapy, medicine.disease, NKG2D, MESH: Neoplasm Metastasis, MESH: Male, MESH: Prospective Studies, [SDV] Life Sciences [q-bio], Killer Cells, Natural, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, MESH: Prostatic Neoplasms, Immunology, Cytokines
Abstract

The field of immunotherapy for solid tumors, such as prostate cancer, has been recently focusing on therapies that can counter tumor-mediated immunosuppression. Precise quantification and characterization of the immune infiltrates in tumors is crucial to improve treatment efficacy. Natural killer (NK) cells, major components of the antitumor immune system, have never been isolated from prostate tumors, despite their suspected role in disease progression. Here, we examined the frequency, phenotype, and functions of NK cells infiltrating control and tumor prostate tissues. NK cell infiltrates in prostate tissues were mainly CD56 (NCAM1)-positive and displayed an unexpected immature, but activated, phenotype with low or no cytotoxic potential. Furthermore, we show that TGFβ1 (TGFB1) is highly secreted into the prostate environment and partly mediates the immunosuppressive effects on NK cells. In addition to this basal level of immunotolerance to NK cells, the prostate environment became further resistant to NK cell–mediated immunity upon cancer cell infiltration. Coculture experiments revealed that prostate cancer cells induced the expression of inhibitory receptor (ILT2/LILRB1) and downregulated the expression of activating receptors NKp46 (NCR1), NKG2D (KLRK1), and CD16 (FCGR3) by NK cells, thus preventing their recognition of tumor cells. Notably, blood levels of NKp46 were also decreased in prostate cancer patients and were inversely correlated with levels of prostate-specific antigen, the main prognostic factor in prostate cancer. Our study shows that a strong immunosuppressive environment impairs NK cell function at multiple levels in prostate cancer and provides a rationale for the design of therapies that restore NK cell efficiency in the prostate tumor microenvironment. Cancer Res; 76(8); 2153–65. ©2016 AACR.

Published
2016

8. Maternal exposure to GOS/inulin mixture prevents food allergies and promotes tolerance in offspring in mice

Author

Michel Neunlist, Philippe Aubert, Laure Castan, Faouzi Braza, Julie Chesné, Antoine Magnan, Marie Bodinier, Grégory Bouchaud, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no 624910, European Project: 267196,EC:FP7:PEOPLE,FP7-PEOPLE-2010-COFUND,AGREENSKILLS(2012), Unité de recherche de l'institut du thorax (ITX-lab), The Enteric Nervous System in gut and brain disorders [U1235] (TENS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE)

Subjects
0301 basic medicine, Allergy, [SDV]Life Sciences [q-bio], Oligosaccharides, MESH: Dietary Supplements, MESH: Inulin, medicine.disease_cause, Mice, chemistry.chemical_compound, Allergen, MESH: Pregnancy, Pregnancy, wheat, Immunology and Allergy, Medicine, MESH: Animals, Intestinal Mucosa, MESH: Maternal Exposure, 2. Zero hunger, Inulin, 3. Good health, Maternal Exposure, Prenatal Exposure Delayed Effects, MESH: Permeability, Allergic response, MESH: Intestinal Mucosa, gut, Female, Food Hypersensitivity, MESH: Lactation, MESH: Immune Tolerance, Offspring, Immunology, Permeability, MESH: Prenatal Exposure Delayed Effects, 03 medical and health sciences, Th2 Cells, Food allergy, MESH: Th2 Cells, Immune Tolerance, microbiota, Animals, Lactation, Weaning, MESH: Microbiota, MESH: Mice, business.industry, medicine.disease, immunity, Disease Models, Animal, 030104 developmental biology, chemistry, Dietary Supplements, MESH: Food Hypersensitivity, symptoms, MESH: Disease Models, Animal, business, MESH: Oligosaccharides, MESH: Female
Abstract

International audience; BACKGROUND: Food allergies affect 4-8% of children and are constantly on the rise, thus making allergies a timely issue. Most importantly, prevention strategies are nonexistent, and current therapeutic strategies have limited efficacy and need to be improved. One alternative to prevent or reduce allergies, particularly during infancy, could consist of modulating maternal immunity and microbiota using nondigestible food ingredients, such as prebiotics. For this purpose, we studied the preventive effects of prebiotics in Balb/c mothers during pregnancy and breastfeeding on food allergy development in offspring mice. METHODS: After weaning, the offspring from mothers that were exposed to GOS/inulin mixture or fed a control diet were intraperitoneally sensitized to wheat proteins to induce a systemic allergic response and orally exposed to the same allergen. Immunological, physiological, and microbial parameters were analyzed. RESULTS: GOS/inulin mixture diet modified the microbiota of mothers and their offspring. Offspring from mothers that received GOS/inulin prebiotics were protected against food allergies and displayed lower clinical scores, specifically of IgE and histamine levels, compared to offspring from mothers fed a control diet. Moreover, GOS/inulin supplementation for the mother resulted in stronger intestinal permeability in the offspring. Enhancement of the regulatory response to allergic inflammation and changes in the Th2/Th1 balance toward a dampened Th2 response were observed in mice from GOS/inulin mixture-exposed mothers. CONCLUSION: The treatment of pregnant and lactating mice with nondigestible GOS/inulin prebiotics promotes a long-term protective effect against food allergies in the offspring.

Published
2016

9. Immune tolerance induction with multiepitope peptide derived from citrullinated autoantigens attenuates arthritis manifestations in adjuvant arthritis rats

Author

Howard Amital, Yehuda Shoenfeld, Smadar Gertel, Guy Serre, Chaim Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University [Tel Aviv], Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), 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), CARBILLET, Véronique, and Tel Aviv University (TAU)

Subjects
Arthritis, MESH: Autoantigens / immunology, Apoptosis, Filaggrin Proteins, Autoantigens, Severity of Illness Index, T-Lymphocytes, Regulatory, Immune tolerance, Arthritis, Rheumatoid, Epitopes, 0302 clinical medicine, MESH: Arthritis, Rheumatoid / immunology, MESH: Citrulline / metabolism, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, T-Lymphocyte Subsets, MESH: Arthritis, Rheumatoid / pathology, Immunology and Allergy, MESH: Animals, MESH: T-Lymphocyte Subsets / metabolism, 0303 health sciences, MESH: Epitopes / metabolism, 3. Good health, Tolerance induction, medicine.anatomical_structure, Phenotype, MESH: Peptides / administration & dosage, MESH: Epitopes / immunology, Rheumatoid arthritis, MESH: T-Lymphocyte Subsets / immunology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, Filaggrin, MESH: Immune Tolerance, MESH: Immunophenotyping, MESH: Rats, Regulatory T cell, MESH: T-Lymphocytes, Regulatory / metabolism, T cell, Immunology, MESH: Autoantibodies / immunology, MESH: Peptides / immunology, MESH: Phenotype, MESH: Autoantigens / metabolism, MESH: Apoptosis / immunology, Immunophenotyping, 03 medical and health sciences, MESH: Severity of Illness Index, medicine, Immune Tolerance, Animals, 030304 developmental biology, Autoantibodies, 030203 arthritis & rheumatology, MESH: Arthritis, Experimental / immunology, business.industry, Autoantibody, medicine.disease, Arthritis, Experimental, Rats, MESH: T-Lymphocytes, Regulatory / immunology, Disease Models, Animal, MESH: Peptides / metabolism, MESH: Epitopes / administration & dosage, MESH: Arthritis, Experimental / pathology, Citrulline, MESH: Disease Models, Animal, business, Peptides, MESH: Female
Abstract

Citrullinated peptides are major targets of disease-specific autoantibodies in rheumatoid arthritis. Currently, citrullinated peptides are used as biomarkers for diagnosing rheumatoid arthritis by measuring anti-citrullinated protein Ab (ACPA) titers in patients’ sera. The accumulation of citrullinated proteins at synovial inflammation sites suggests that they are possible targets for tolerance induction. The objective of the present study was to determine whether citrullinated peptides could induce tolerance in an experimental arthritis model in rats. In view of the multiplicity of target citrullinated autoantigens described for ACPA, we generated a multiepitope citrullinated peptide (Cit-ME), derived from major prevalent citrullinated autoantigens (citrullinated filaggrin, fibrinogen, vimentin, and collagen type II), and studied its effects on arthritic rats. Adjuvant-induced arthritis was induced in Lewis rats. Beginning at day 7 after disease induction, the rats received eight s.c. injections of Cit-ME on alternate days. Differences in clinical status and modulation of T cell populations were analyzed. In adjuvant-induced arthritis rats treated with Cit-ME, disease severity was significantly reduced compared with that of untreated rats. Moreover, amelioration of disease manifestations was related to an increased regulatory T cell subset and an elevated apoptosis rate of T cells associated with reduced Th17 cells. Thus, the use of citrullinated peptides–based immunotherapy may be a promising approach for tolerance induction in experimental arthritis and perhaps even in susceptible individuals that are ACPA-seropositive in human arthritis.

Published
2014

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