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