Local Modulation of Antigen-Presenting Cell Development after Resolution of Pneumonia Induces Long-Term Susceptibility to Secondary Infections.
Identifieur interne : 000884 ( Main/Exploration ); précédent : 000883; suivant : 000885Local Modulation of Antigen-Presenting Cell Development after Resolution of Pneumonia Induces Long-Term Susceptibility to Secondary Infections.
Auteurs : Antoine Roquilly [France] ; Hamish E G. Mcwilliam [Australie] ; Cedric Jacqueline [France] ; Zehua Tian [Australie] ; Raphael Cinotti [France] ; Marie Rimbert [France] ; Linda Wakim [Australie] ; Irina Caminschi [Australie] ; Mireille H. Lahoud [Australie] ; Gabrielle T. Belz [Australie] ; Axel Kallies [Australie] ; Justine D. Mintern [Australie] ; Karim Asehnoune [France] ; Jose A. Villadangos [Australie]Source :
- Immunity [ 1097-4180 ] ; 2017.
Descripteurs français
- KwdFr :
- Adulte d'âge moyen, Animaux, Cellules cultivées, Cellules dendritiques (immunologie), Différenciation cellulaire, Escherichia coli, Facteur de croissance transformant bêta (génétique), Facteur de croissance transformant bêta (métabolisme), Facteurs de régulation d'interféron (génétique), Facteurs de régulation d'interféron (métabolisme), Facteurs de transcription (génétique), Facteurs de transcription (métabolisme), Femelle, Humains, Infections à Escherichia coli (immunologie), Infections à Orthomyxoviridae (immunologie), Lymphocytes T régulateurs (immunologie), Macrophages (immunologie), Mâle, Pneumopathie infectieuse (immunologie), Présentation d'antigène, Sepsie (immunologie), Souris, Souris de lignée C57BL, Souris knockout, Sujet âgé, Tolérance immunitaire, Virus de la grippe A (immunologie).
- MESH :
- génétique : Facteur de croissance transformant bêta, Facteurs de régulation d'interféron, Facteurs de transcription.
- immunologie : Cellules dendritiques, Infections à Escherichia coli, Infections à Orthomyxoviridae, Lymphocytes T régulateurs, Macrophages, Pneumopathie infectieuse, Sepsie, Virus de la grippe A.
- métabolisme : Facteur de croissance transformant bêta, Facteurs de régulation d'interféron, Facteurs de transcription.
- Adulte d'âge moyen, Animaux, Cellules cultivées, Différenciation cellulaire, Escherichia coli, Femelle, Humains, Mâle, Présentation d'antigène, Souris, Souris de lignée C57BL, Souris knockout, Sujet âgé, Tolérance immunitaire.
English descriptors
- KwdEn :
- Aged, Animals, Antigen Presentation, Cell Differentiation, Cells, Cultured, Dendritic Cells (immunology), Escherichia coli, Escherichia coli Infections (immunology), Female, Humans, Immune Tolerance, Influenza A virus (immunology), Interferon Regulatory Factors (genetics), Interferon Regulatory Factors (metabolism), Macrophages (immunology), Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Middle Aged, Orthomyxoviridae Infections (immunology), Pneumonia (immunology), Sepsis (immunology), T-Lymphocytes, Regulatory (immunology), Transcription Factors (genetics), Transcription Factors (metabolism), Transforming Growth Factor beta (genetics), Transforming Growth Factor beta (metabolism).
- MESH :
- chemical , genetics : Interferon Regulatory Factors, Transcription Factors, Transforming Growth Factor beta.
- immunology : Dendritic Cells, Escherichia coli Infections, Influenza A virus, Macrophages, Orthomyxoviridae Infections, Pneumonia, Sepsis, T-Lymphocytes, Regulatory.
- chemical , metabolism : Interferon Regulatory Factors, Transcription Factors, Transforming Growth Factor beta.
- Aged, Animals, Antigen Presentation, Cell Differentiation, Cells, Cultured, Escherichia coli, Female, Humans, Immune Tolerance, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Middle Aged.
Abstract
Lung infections cause prolonged immune alterations and elevated susceptibility to secondary pneumonia. We found that, after resolution of primary viral or bacterial pneumonia, dendritic cells (DC), and macrophages exhibited poor antigen-presentation capacity and secretion of immunogenic cytokines. Development of these "paralyzed" DCs and macrophages depended on the immunosuppressive microenvironment established upon resolution of primary infection, which involved regulatory T (Treg) cells and the cytokine TGF-β. Paralyzed DCs secreted TGF-β and induced local Treg cell accumulation. They also expressed lower amounts of IRF4, a transcription factor associated with increased antigen-presentation capacity, and higher amounts of Blimp1, a transcription factor associated with tolerogenic functions, than DCs present during primary infection. Blimp1 expression in DC of humans suffering sepsis or trauma correlated with severity and complicated outcomes. Our findings describe mechanisms underlying sepsis- and trauma-induced immunosuppression, reveal prognostic markers of susceptibility to secondary infections and identify potential targets for therapeutic intervention.
DOI: 10.1016/j.immuni.2017.06.021
PubMed: 28723546
Affiliations:
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Surgical Intensive Care Unit, Hotel Dieu, University Hospital of Nantes, 44093 Nantes, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>EA3826 Thérapeutiques Anti-Infectieuses, Institut de Recherche en Santé 2 Nantes Biotech, Medical University of Nantes, 44000 Nantes, France; Surgical Intensive Care Unit, Hotel Dieu, University Hospital of Nantes, 44093 Nantes</wicri:regionArea><wicri:noRegion>44093 Nantes</wicri:noRegion><wicri:noRegion>44093 Nantes</wicri:noRegion></affiliation></author><author><name sortKey="Rimbert, Marie" sort="Rimbert, Marie" uniqKey="Rimbert M" first="Marie" last="Rimbert">Marie Rimbert</name><affiliation wicri:level="3"><nlm:affiliation>CHU Nantes, Laboratoire d'immunologie, Center for Immuno-Monitoring Nantes Atlantic (CIMNA), Laboratoire d'Immunologie, CHU de Nantes, Nantes, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CHU Nantes, Laboratoire d'immunologie, Center for Immuno-Monitoring Nantes Atlantic (CIMNA), Laboratoire d'Immunologie, CHU de Nantes, Nantes</wicri:regionArea><placeName><region type="region">Pays de la Loire</region><region type="old region">Pays de la Loire</region><settlement type="city">Nantes</settlement></placeName></affiliation></author><author><name sortKey="Wakim, Linda" sort="Wakim, Linda" uniqKey="Wakim L" first="Linda" last="Wakim">Linda Wakim</name><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, Doherty Institute of Infection and Immunity, The University of Melbourne, Parkville, Victoria 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology, Doherty Institute of Infection and Immunity, The University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Caminschi, Irina" sort="Caminschi, Irina" uniqKey="Caminschi I" first="Irina" last="Caminschi">Irina Caminschi</name><affiliation wicri:level="1"><nlm:affiliation>Infection & Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Infection & Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800</wicri:regionArea><wicri:noRegion>VIC 3800</wicri:noRegion></affiliation></author><author><name sortKey="Lahoud, Mireille H" sort="Lahoud, Mireille H" uniqKey="Lahoud M" first="Mireille H" last="Lahoud">Mireille H. 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Belz</name><affiliation wicri:level="4"><nlm:affiliation>The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, Victoria, 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, Victoria, 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Kallies, Axel" sort="Kallies, Axel" uniqKey="Kallies A" first="Axel" last="Kallies">Axel Kallies</name><affiliation wicri:level="4"><nlm:affiliation>The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, Victoria, 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, Victoria, 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Mintern, Justine D" sort="Mintern, Justine D" uniqKey="Mintern J" first="Justine D" last="Mintern">Justine D. Mintern</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Asehnoune, Karim" sort="Asehnoune, Karim" uniqKey="Asehnoune K" first="Karim" last="Asehnoune">Karim Asehnoune</name><affiliation wicri:level="1"><nlm:affiliation>EA3826 Thérapeutiques Anti-Infectieuses, Institut de Recherche en Santé 2 Nantes Biotech, Medical University of Nantes, 44000 Nantes, France; Surgical Intensive Care Unit, Hotel Dieu, University Hospital of Nantes, 44093 Nantes, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>EA3826 Thérapeutiques Anti-Infectieuses, Institut de Recherche en Santé 2 Nantes Biotech, Medical University of Nantes, 44000 Nantes, France; Surgical Intensive Care Unit, Hotel Dieu, University Hospital of Nantes, 44093 Nantes</wicri:regionArea><wicri:noRegion>44093 Nantes</wicri:noRegion><wicri:noRegion>44093 Nantes</wicri:noRegion></affiliation></author><author><name sortKey="Villadangos, Jose A" sort="Villadangos, Jose A" uniqKey="Villadangos J" first="Jose A" last="Villadangos">Jose A. Villadangos</name><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, Doherty Institute of Infection and Immunity, The University of Melbourne, Parkville, Victoria 3010, Australia; Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia. Electronic address: j.villadangos@unimelb.edu.au.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology, Doherty Institute of Infection and Immunity, The University of Melbourne, Parkville, Victoria 3010, Australia; Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:28723546</idno><idno type="pmid">28723546</idno><idno type="doi">10.1016/j.immuni.2017.06.021</idno><idno type="wicri:Area/PubMed/Corpus">000868</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000868</idno><idno type="wicri:Area/PubMed/Curation">000865</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000865</idno><idno type="wicri:Area/PubMed/Checkpoint">000865</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000865</idno><idno type="wicri:Area/Ncbi/Merge">004B47</idno><idno type="wicri:Area/Ncbi/Curation">004B47</idno><idno type="wicri:Area/Ncbi/Checkpoint">004B47</idno><idno type="wicri:Area/Main/Merge">000879</idno><idno type="wicri:Area/Main/Curation">000884</idno><idno type="wicri:Area/Main/Exploration">000884</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Local Modulation of Antigen-Presenting Cell Development after Resolution of Pneumonia Induces Long-Term Susceptibility to Secondary Infections.</title><author><name sortKey="Roquilly, Antoine" sort="Roquilly, Antoine" uniqKey="Roquilly A" first="Antoine" last="Roquilly">Antoine Roquilly</name><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, Doherty Institute of Infection and Immunity, The University of Melbourne, Parkville, Victoria 3010, Australia; EA3826 Thérapeutiques Anti-Infectieuses, Institut de Recherche en Santé 2 Nantes Biotech, Medical University of Nantes, 44000 Nantes, France; Surgical Intensive Care Unit, Hotel Dieu, University Hospital of Nantes, 44093 Nantes, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Microbiology and Immunology, Doherty Institute of Infection and Immunity, The University of Melbourne, Parkville, Victoria 3010, Australia; EA3826 Thérapeutiques Anti-Infectieuses, Institut de Recherche en Santé 2 Nantes Biotech, Medical University of Nantes, 44000 Nantes, France; Surgical Intensive Care Unit, Hotel Dieu, University Hospital of Nantes, 44093 Nantes</wicri:regionArea><placeName><region type="region" nuts="2">Pays de la Loire</region><settlement type="city">Nantes</settlement><settlement type="city">Melbourne</settlement></placeName><orgName type="university">Université de Melbourne</orgName></affiliation></author><author><name sortKey="Mcwilliam, Hamish E G" sort="Mcwilliam, Hamish E G" uniqKey="Mcwilliam H" first="Hamish E G" last="Mcwilliam">Hamish E G. Mcwilliam</name><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, Doherty Institute of Infection and Immunity, The University of Melbourne, Parkville, Victoria 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology, Doherty Institute of Infection and Immunity, The University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Jacqueline, Cedric" sort="Jacqueline, Cedric" uniqKey="Jacqueline C" first="Cedric" last="Jacqueline">Cedric Jacqueline</name><affiliation wicri:level="1"><nlm:affiliation>EA3826 Thérapeutiques Anti-Infectieuses, Institut de Recherche en Santé 2 Nantes Biotech, Medical University of Nantes, 44000 Nantes, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>EA3826 Thérapeutiques Anti-Infectieuses, Institut de Recherche en Santé 2 Nantes Biotech, Medical University of Nantes, 44000 Nantes</wicri:regionArea><wicri:noRegion>44000 Nantes</wicri:noRegion><wicri:noRegion>44000 Nantes</wicri:noRegion></affiliation></author><author><name sortKey="Tian, Zehua" sort="Tian, Zehua" uniqKey="Tian Z" first="Zehua" last="Tian">Zehua Tian</name><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, Doherty Institute of Infection and Immunity, The University of Melbourne, Parkville, Victoria 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology, Doherty Institute of Infection and Immunity, The University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Cinotti, Raphael" sort="Cinotti, Raphael" uniqKey="Cinotti R" first="Raphael" last="Cinotti">Raphael Cinotti</name><affiliation wicri:level="1"><nlm:affiliation>EA3826 Thérapeutiques Anti-Infectieuses, Institut de Recherche en Santé 2 Nantes Biotech, Medical University of Nantes, 44000 Nantes, France; Surgical Intensive Care Unit, Hotel Dieu, University Hospital of Nantes, 44093 Nantes, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>EA3826 Thérapeutiques Anti-Infectieuses, Institut de Recherche en Santé 2 Nantes Biotech, Medical University of Nantes, 44000 Nantes, France; Surgical Intensive Care Unit, Hotel Dieu, University Hospital of Nantes, 44093 Nantes</wicri:regionArea><wicri:noRegion>44093 Nantes</wicri:noRegion><wicri:noRegion>44093 Nantes</wicri:noRegion></affiliation></author><author><name sortKey="Rimbert, Marie" sort="Rimbert, Marie" uniqKey="Rimbert M" first="Marie" last="Rimbert">Marie Rimbert</name><affiliation wicri:level="3"><nlm:affiliation>CHU Nantes, Laboratoire d'immunologie, Center for Immuno-Monitoring Nantes Atlantic (CIMNA), Laboratoire d'Immunologie, CHU de Nantes, Nantes, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CHU Nantes, Laboratoire d'immunologie, Center for Immuno-Monitoring Nantes Atlantic (CIMNA), Laboratoire d'Immunologie, CHU de Nantes, Nantes</wicri:regionArea><placeName><region type="region">Pays de la Loire</region><region type="old region">Pays de la Loire</region><settlement type="city">Nantes</settlement></placeName></affiliation></author><author><name sortKey="Wakim, Linda" sort="Wakim, Linda" uniqKey="Wakim L" first="Linda" last="Wakim">Linda Wakim</name><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, Doherty Institute of Infection and Immunity, The University of Melbourne, Parkville, Victoria 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology, Doherty Institute of Infection and Immunity, The University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Caminschi, Irina" sort="Caminschi, Irina" uniqKey="Caminschi I" first="Irina" last="Caminschi">Irina Caminschi</name><affiliation wicri:level="1"><nlm:affiliation>Infection & Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Infection & Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800</wicri:regionArea><wicri:noRegion>VIC 3800</wicri:noRegion></affiliation></author><author><name sortKey="Lahoud, Mireille H" sort="Lahoud, Mireille H" uniqKey="Lahoud M" first="Mireille H" last="Lahoud">Mireille H. Lahoud</name><affiliation wicri:level="1"><nlm:affiliation>Infection & Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Infection & Immunity Program, Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800</wicri:regionArea><wicri:noRegion>VIC 3800</wicri:noRegion></affiliation></author><author><name sortKey="Belz, Gabrielle T" sort="Belz, Gabrielle T" uniqKey="Belz G" first="Gabrielle T" last="Belz">Gabrielle T. Belz</name><affiliation wicri:level="4"><nlm:affiliation>The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, Victoria, 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, Victoria, 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Kallies, Axel" sort="Kallies, Axel" uniqKey="Kallies A" first="Axel" last="Kallies">Axel Kallies</name><affiliation wicri:level="4"><nlm:affiliation>The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, Victoria, 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; The Department of Medical Biology, University of Melbourne, Parkville, Victoria, 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Mintern, Justine D" sort="Mintern, Justine D" uniqKey="Mintern J" first="Justine D" last="Mintern">Justine D. Mintern</name><affiliation wicri:level="4"><nlm:affiliation>Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Asehnoune, Karim" sort="Asehnoune, Karim" uniqKey="Asehnoune K" first="Karim" last="Asehnoune">Karim Asehnoune</name><affiliation wicri:level="1"><nlm:affiliation>EA3826 Thérapeutiques Anti-Infectieuses, Institut de Recherche en Santé 2 Nantes Biotech, Medical University of Nantes, 44000 Nantes, France; Surgical Intensive Care Unit, Hotel Dieu, University Hospital of Nantes, 44093 Nantes, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>EA3826 Thérapeutiques Anti-Infectieuses, Institut de Recherche en Santé 2 Nantes Biotech, Medical University of Nantes, 44000 Nantes, France; Surgical Intensive Care Unit, Hotel Dieu, University Hospital of Nantes, 44093 Nantes</wicri:regionArea><wicri:noRegion>44093 Nantes</wicri:noRegion><wicri:noRegion>44093 Nantes</wicri:noRegion></affiliation></author><author><name sortKey="Villadangos, Jose A" sort="Villadangos, Jose A" uniqKey="Villadangos J" first="Jose A" last="Villadangos">Jose A. Villadangos</name><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, Doherty Institute of Infection and Immunity, The University of Melbourne, Parkville, Victoria 3010, Australia; Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia. Electronic address: j.villadangos@unimelb.edu.au.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology, Doherty Institute of Infection and Immunity, The University of Melbourne, Parkville, Victoria 3010, Australia; Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author></analytic><series><title level="j">Immunity</title><idno type="eISSN">1097-4180</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Animals</term><term>Antigen Presentation</term><term>Cell Differentiation</term><term>Cells, Cultured</term><term>Dendritic Cells (immunology)</term><term>Escherichia coli</term><term>Escherichia coli Infections (immunology)</term><term>Female</term><term>Humans</term><term>Immune Tolerance</term><term>Influenza A virus (immunology)</term><term>Interferon Regulatory Factors (genetics)</term><term>Interferon Regulatory Factors (metabolism)</term><term>Macrophages (immunology)</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Knockout</term><term>Middle Aged</term><term>Orthomyxoviridae Infections (immunology)</term><term>Pneumonia (immunology)</term><term>Sepsis (immunology)</term><term>T-Lymphocytes, Regulatory (immunology)</term><term>Transcription Factors (genetics)</term><term>Transcription Factors (metabolism)</term><term>Transforming Growth Factor beta (genetics)</term><term>Transforming Growth Factor beta (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte d'âge moyen</term><term>Animaux</term><term>Cellules cultivées</term><term>Cellules dendritiques (immunologie)</term><term>Différenciation cellulaire</term><term>Escherichia coli</term><term>Facteur de croissance transformant bêta (génétique)</term><term>Facteur de croissance transformant bêta (métabolisme)</term><term>Facteurs de régulation d'interféron (génétique)</term><term>Facteurs de régulation d'interféron (métabolisme)</term><term>Facteurs de transcription (génétique)</term><term>Facteurs de transcription (métabolisme)</term><term>Femelle</term><term>Humains</term><term>Infections à Escherichia coli (immunologie)</term><term>Infections à Orthomyxoviridae (immunologie)</term><term>Lymphocytes T régulateurs (immunologie)</term><term>Macrophages (immunologie)</term><term>Mâle</term><term>Pneumopathie infectieuse (immunologie)</term><term>Présentation d'antigène</term><term>Sepsie (immunologie)</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Souris knockout</term><term>Sujet âgé</term><term>Tolérance immunitaire</term><term>Virus de la grippe A (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Interferon Regulatory Factors</term><term>Transcription Factors</term><term>Transforming Growth Factor beta</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Facteur de croissance transformant bêta</term><term>Facteurs de régulation d'interféron</term><term>Facteurs de transcription</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Cellules dendritiques</term><term>Infections à Escherichia coli</term><term>Infections à Orthomyxoviridae</term><term>Lymphocytes T régulateurs</term><term>Macrophages</term><term>Pneumopathie infectieuse</term><term>Sepsie</term><term>Virus de la grippe A</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Dendritic Cells</term><term>Escherichia coli Infections</term><term>Influenza A virus</term><term>Macrophages</term><term>Orthomyxoviridae Infections</term><term>Pneumonia</term><term>Sepsis</term><term>T-Lymphocytes, Regulatory</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Interferon Regulatory Factors</term><term>Transcription Factors</term><term>Transforming Growth Factor beta</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Facteur de croissance transformant bêta</term><term>Facteurs de régulation d'interféron</term><term>Facteurs de transcription</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Animals</term><term>Antigen Presentation</term><term>Cell Differentiation</term><term>Cells, Cultured</term><term>Escherichia coli</term><term>Female</term><term>Humans</term><term>Immune Tolerance</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Knockout</term><term>Middle Aged</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte d'âge moyen</term><term>Animaux</term><term>Cellules cultivées</term><term>Différenciation cellulaire</term><term>Escherichia coli</term><term>Femelle</term><term>Humains</term><term>Mâle</term><term>Présentation d'antigène</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Souris knockout</term><term>Sujet âgé</term><term>Tolérance immunitaire</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Lung infections cause prolonged immune alterations and elevated susceptibility to secondary pneumonia. We found that, after resolution of primary viral or bacterial pneumonia, dendritic cells (DC), and macrophages exhibited poor antigen-presentation capacity and secretion of immunogenic cytokines. Development of these "paralyzed" DCs and macrophages depended on the immunosuppressive microenvironment established upon resolution of primary infection, which involved regulatory T (Treg) cells and the cytokine TGF-β. Paralyzed DCs secreted TGF-β and induced local Treg cell accumulation. They also expressed lower amounts of IRF4, a transcription factor associated with increased antigen-presentation capacity, and higher amounts of Blimp1, a transcription factor associated with tolerogenic functions, than DCs present during primary infection. Blimp1 expression in DC of humans suffering sepsis or trauma correlated with severity and complicated outcomes. Our findings describe mechanisms underlying sepsis- and trauma-induced immunosuppression, reveal prognostic markers of susceptibility to secondary infections and identify potential targets for therapeutic intervention.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li></country><region><li>Pays de la Loire</li><li>Victoria (État)</li></region><settlement><li>Melbourne</li><li>Nantes</li></settlement><orgName><li>Université de Melbourne</li></orgName></list><tree><country name="France"><region name="Pays de la Loire"><name sortKey="Roquilly, Antoine" sort="Roquilly, Antoine" uniqKey="Roquilly A" first="Antoine" last="Roquilly">Antoine Roquilly</name></region><name sortKey="Asehnoune, Karim" sort="Asehnoune, Karim" uniqKey="Asehnoune K" first="Karim" last="Asehnoune">Karim Asehnoune</name><name sortKey="Cinotti, Raphael" sort="Cinotti, Raphael" uniqKey="Cinotti R" first="Raphael" last="Cinotti">Raphael Cinotti</name><name sortKey="Jacqueline, Cedric" sort="Jacqueline, Cedric" uniqKey="Jacqueline C" first="Cedric" last="Jacqueline">Cedric Jacqueline</name><name sortKey="Rimbert, Marie" sort="Rimbert, Marie" uniqKey="Rimbert M" first="Marie" last="Rimbert">Marie Rimbert</name></country><country name="Australie"><region name="Victoria (État)"><name sortKey="Mcwilliam, Hamish E G" sort="Mcwilliam, Hamish E G" uniqKey="Mcwilliam H" first="Hamish E G" last="Mcwilliam">Hamish E G. Mcwilliam</name></region><name sortKey="Belz, Gabrielle T" sort="Belz, Gabrielle T" uniqKey="Belz G" first="Gabrielle T" last="Belz">Gabrielle T. Belz</name><name sortKey="Caminschi, Irina" sort="Caminschi, Irina" uniqKey="Caminschi I" first="Irina" last="Caminschi">Irina Caminschi</name><name sortKey="Kallies, Axel" sort="Kallies, Axel" uniqKey="Kallies A" first="Axel" last="Kallies">Axel Kallies</name><name sortKey="Lahoud, Mireille H" sort="Lahoud, Mireille H" uniqKey="Lahoud M" first="Mireille H" last="Lahoud">Mireille H. Lahoud</name><name sortKey="Mintern, Justine D" sort="Mintern, Justine D" uniqKey="Mintern J" first="Justine D" last="Mintern">Justine D. Mintern</name><name sortKey="Tian, Zehua" sort="Tian, Zehua" uniqKey="Tian Z" first="Zehua" last="Tian">Zehua Tian</name><name sortKey="Villadangos, Jose A" sort="Villadangos, Jose A" uniqKey="Villadangos J" first="Jose A" last="Villadangos">Jose A. Villadangos</name><name sortKey="Wakim, Linda" sort="Wakim, Linda" uniqKey="Wakim L" first="Linda" last="Wakim">Linda Wakim</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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