The Microbiota Mediates Pathogen Clearance from the Gut Lumen after Non-Typhoidal Salmonella Diarrhea
Identifieur interne : 006E70 ( Main/Exploration ); précédent : 006E69; suivant : 006E71The Microbiota Mediates Pathogen Clearance from the Gut Lumen after Non-Typhoidal Salmonella Diarrhea
Auteurs : Kathrin Endt [Suisse] ; B Rbel Stecher [Suisse] ; Samuel Chaffron [Suisse] ; Emma Slack [Suisse] ; Nicolas Tchitchek [France] ; Arndt Benecke [France] ; Laurye Van Maele [France] ; Jean-Claude Sirard [France] ; Andreas J. Mueller [Suisse] ; Mathias Heikenwalder [Suisse] ; Andrew J. Macpherson [Suisse] ; Richard Strugnell [Australie] ; Christian Von Mering [Suisse] ; Wolf-Dietrich Hardt [Suisse]Source :
- PLoS Pathogens [ 1553-7366 ] ; 2010.
Abstract
Many enteropathogenic bacteria target the mammalian gut. The mechanisms protecting the host from infection are poorly understood. We have studied the protective functions of secretory antibodies (sIgA) and the microbiota, using a mouse model for
Url:
DOI: 10.1371/journal.ppat.1001097
PubMed: 20844578
PubMed Central: 2936549
Affiliations:
- Australie, France, Suisse
- Canton de Berne, Canton de Zurich, Hauts-de-France, Nord-Pas-de-Calais, Victoria (État)
- Berne, Lille, Melbourne, Zurich
- Université de Melbourne, Université de Zurich
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Endt</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Institute of Microbiology, ETH Zürich, Zürich, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Microbiology, ETH Zürich, Zürich</wicri:regionArea><placeName><settlement type="city">Zurich</settlement><region nuts="3" type="region">Canton de Zurich</region></placeName></affiliation></author><author><name sortKey="Stecher, B Rbel" sort="Stecher, B Rbel" uniqKey="Stecher B" first="B Rbel" last="Stecher">B Rbel Stecher</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Institute of Microbiology, ETH Zürich, Zürich, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Microbiology, ETH Zürich, Zürich</wicri:regionArea><placeName><settlement type="city">Zurich</settlement><region nuts="3" type="region">Canton de Zurich</region></placeName></affiliation></author><author><name sortKey="Chaffron, Samuel" sort="Chaffron, Samuel" uniqKey="Chaffron S" first="Samuel" last="Chaffron">Samuel Chaffron</name><affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>Institute of Molecular Biology and Swiss Institute of Bioinformatics, University of Zürich, Zürich, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Molecular Biology and Swiss Institute of Bioinformatics, University of Zürich, Zürich</wicri:regionArea><placeName><settlement type="city">Zurich</settlement><region nuts="3" type="region">Canton de Zurich</region><settlement type="city">Zurich</settlement></placeName><orgName type="university">Université de Zurich</orgName></affiliation></author><author><name sortKey="Slack, Emma" sort="Slack, Emma" uniqKey="Slack E" first="Emma" last="Slack">Emma Slack</name><affiliation wicri:level="3"><nlm:aff id="aff3"><addr-line>Gastroenterology Inselspital, Department Klinische Forschung, Bern, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Gastroenterology Inselspital, Department Klinische Forschung, Bern</wicri:regionArea><placeName><settlement type="city">Berne</settlement><region type="région" nuts="3">Canton de Berne</region></placeName></affiliation></author><author><name sortKey="Tchitchek, Nicolas" sort="Tchitchek, Nicolas" uniqKey="Tchitchek N" first="Nicolas" last="Tchitchek">Nicolas Tchitchek</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Institut des Hautes Études Scientifiques & CNRS USR3078, Bures sur Yvette, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut des Hautes Études Scientifiques & CNRS USR3078, Bures sur Yvette</wicri:regionArea><wicri:noRegion>Bures sur Yvette</wicri:noRegion><wicri:noRegion>Bures sur Yvette</wicri:noRegion></affiliation></author><author><name sortKey="Benecke, Arndt" sort="Benecke, Arndt" uniqKey="Benecke A" first="Arndt" last="Benecke">Arndt Benecke</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Institut des Hautes Études Scientifiques & CNRS USR3078, Bures sur Yvette, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut des Hautes Études Scientifiques & CNRS USR3078, Bures sur Yvette</wicri:regionArea><wicri:noRegion>Bures sur Yvette</wicri:noRegion><wicri:noRegion>Bures sur Yvette</wicri:noRegion></affiliation></author><author><name sortKey="Van Maele, Laurye" sort="Van Maele, Laurye" uniqKey="Van Maele L" first="Laurye" last="Van Maele">Laurye Van Maele</name><affiliation wicri:level="3"><nlm:aff id="aff5"><addr-line>Institut National de la Santé et de la Recherche Médicale, U801; Institut Pasteur de Lille; Univ. Lille Nord de France, UDSL, Lille, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, U801; Institut Pasteur de Lille; Univ. Lille Nord de France, UDSL, Lille</wicri:regionArea><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Sirard, Jean Claude" sort="Sirard, Jean Claude" uniqKey="Sirard J" first="Jean-Claude" last="Sirard">Jean-Claude Sirard</name><affiliation wicri:level="3"><nlm:aff id="aff5"><addr-line>Institut National de la Santé et de la Recherche Médicale, U801; Institut Pasteur de Lille; Univ. Lille Nord de France, UDSL, Lille, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, U801; Institut Pasteur de Lille; Univ. Lille Nord de France, UDSL, Lille</wicri:regionArea><placeName><region type="region">Hauts-de-France</region><region type="old region">Nord-Pas-de-Calais</region><settlement type="city">Lille</settlement></placeName></affiliation></author><author><name sortKey="Mueller, Andreas J" sort="Mueller, Andreas J" uniqKey="Mueller A" first="Andreas J." last="Mueller">Andreas J. Mueller</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Institute of Microbiology, ETH Zürich, Zürich, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Microbiology, ETH Zürich, Zürich</wicri:regionArea><placeName><settlement type="city">Zurich</settlement><region nuts="3" type="region">Canton de Zurich</region></placeName></affiliation></author><author><name sortKey="Heikenwalder, Mathias" sort="Heikenwalder, Mathias" uniqKey="Heikenwalder M" first="Mathias" last="Heikenwalder">Mathias Heikenwalder</name><affiliation wicri:level="3"><nlm:aff id="aff6"><addr-line>Institute of Neuropathology, University Hospital of Zurich, Zürich, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Neuropathology, University Hospital of Zurich, Zürich</wicri:regionArea><placeName><settlement type="city">Zurich</settlement><region nuts="3" type="region">Canton de Zurich</region></placeName></affiliation></author><author><name sortKey="Macpherson, Andrew J" sort="Macpherson, Andrew J" uniqKey="Macpherson A" first="Andrew J." last="Macpherson">Andrew J. Macpherson</name><affiliation wicri:level="3"><nlm:aff id="aff3"><addr-line>Gastroenterology Inselspital, Department Klinische Forschung, Bern, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Gastroenterology Inselspital, Department Klinische Forschung, Bern</wicri:regionArea><placeName><settlement type="city">Berne</settlement><region type="région" nuts="3">Canton de Berne</region></placeName></affiliation></author><author><name sortKey="Strugnell, Richard" sort="Strugnell, Richard" uniqKey="Strugnell R" first="Richard" last="Strugnell">Richard Strugnell</name><affiliation wicri:level="4"><nlm:aff id="aff7"><addr-line>Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria</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="Von Mering, Christian" sort="Von Mering, Christian" uniqKey="Von Mering C" first="Christian" last="Von Mering">Christian Von Mering</name><affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>Institute of Molecular Biology and Swiss Institute of Bioinformatics, University of Zürich, Zürich, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Molecular Biology and Swiss Institute of Bioinformatics, University of Zürich, Zürich</wicri:regionArea><placeName><settlement type="city">Zurich</settlement><region nuts="3" type="region">Canton de Zurich</region><settlement type="city">Zurich</settlement></placeName><orgName type="university">Université de Zurich</orgName></affiliation></author><author><name sortKey="Hardt, Wolf Dietrich" sort="Hardt, Wolf Dietrich" uniqKey="Hardt W" first="Wolf-Dietrich" last="Hardt">Wolf-Dietrich Hardt</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Institute of Microbiology, ETH Zürich, Zürich, Switzerland</addr-line></nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>Institute of Microbiology, ETH Zürich, Zürich</wicri:regionArea><placeName><settlement type="city">Zurich</settlement><region nuts="3" type="region">Canton de Zurich</region></placeName></affiliation></author></analytic><series><title level="j">PLoS Pathogens</title><idno type="ISSN">1553-7366</idno><idno type="eISSN">1553-7374</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Many enteropathogenic bacteria target the mammalian gut. The mechanisms protecting the host from infection are poorly understood. We have studied the protective functions of secretory antibodies (sIgA) and the microbiota, using a mouse model for <italic>S. typhimurium</italic> diarrhea. This pathogen is a common cause of diarrhea in humans world-wide. <italic>S. typhimurium</italic> (<italic>S. tm</italic><sup>att</sup>, <italic>sseD</italic>) causes a self-limiting gut infection in streptomycin-treated mice. After 40 days, all animals had overcome the disease, developed a sIgA response, and most had cleared the pathogen from the gut lumen. sIgA limited pathogen access to the mucosal surface and protected from gut inflammation in challenge infections. This protection was O-antigen specific, as demonstrated with pathogens lacking the <italic>S. typhimurium</italic> O-antigen (<italic>wbaP</italic>, <italic>S. enteritidis</italic>) and sIgA-deficient mice (TCRβ<sup>−/−</sup>δ<sup>−/−</sup>, J<sub>H</sub><sup>−/−</sup>, IgA<sup>−/−</sup>, pIgR<sup>−/−</sup>). Surprisingly, sIgA-deficiency did not affect the kinetics of pathogen clearance from the gut lumen. Instead, this was mediated by the microbiota. This was confirmed using ‘L-mice’ which harbor a low complexity gut flora, lack colonization resistance and develop a normal sIgA response, but fail to clear <italic>S. tm</italic><sup>att</sup> from the gut lumen. In these mice, pathogen clearance was achieved by transferring a normal complex microbiota. Thus, besides colonization resistance ( = pathogen blockage by an intact microbiota), the microbiota mediates a second, novel protective function, i.e. pathogen clearance. Here, the normal microbiota re-grows from a state of depletion and disturbed composition and gradually clears even very high pathogen loads from the gut lumen, a site inaccessible to most “classical” immune effector mechanisms. In conclusion, sIgA and microbiota serve complementary protective functions. The microbiota confers colonization resistance and mediates pathogen clearance in primary infections, while sIgA protects from disease if the host re-encounters the same pathogen. This has implications for curing <italic>S. typhimurium</italic> diarrhea and for preventing transmission.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Backhed, F" uniqKey="Backhed F">F Backhed</name></author><author><name sortKey="Ley, Re" uniqKey="Ley R">RE Ley</name></author><author><name sortKey="Sonnenburg, Jl" uniqKey="Sonnenburg J">JL Sonnenburg</name></author><author><name sortKey="Peterson, Da" uniqKey="Peterson D">DA Peterson</name></author><author><name sortKey="Gordon, Ji" uniqKey="Gordon J">JI Gordon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ivanov, Ii" uniqKey="Ivanov I">II Ivanov</name></author><author><name sortKey="Atarashi, K" uniqKey="Atarashi K">K Atarashi</name></author><author><name sortKey="Manel, N" uniqKey="Manel N">N Manel</name></author><author><name sortKey="Brodie, El" uniqKey="Brodie E">EL Brodie</name></author><author><name sortKey="Shima, T" 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J">J Fish</name></author><author><name sortKey="Chai, B" uniqKey="Chai B">B Chai</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, Q" uniqKey="Wang Q">Q Wang</name></author><author><name sortKey="Garrity, Gm" uniqKey="Garrity G">GM Garrity</name></author><author><name sortKey="Tiedje, Jm" uniqKey="Tiedje J">JM Tiedje</name></author><author><name sortKey="Cole, Jr" uniqKey="Cole J">JR Cole</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sogin, Ml" uniqKey="Sogin M">ML Sogin</name></author><author><name sortKey="Morrison, Hg" uniqKey="Morrison H">HG Morrison</name></author><author><name sortKey="Huber, Ja" uniqKey="Huber J">JA Huber</name></author><author><name sortKey="Welch, Dm" uniqKey="Welch D">DM Welch</name></author><author><name sortKey="Huse, Sm" uniqKey="Huse S">SM Huse</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Quince, C" uniqKey="Quince C">C Quince</name></author><author><name sortKey="Lanzen, A" uniqKey="Lanzen A">A Lanzen</name></author><author><name sortKey="Curtis, Tp" uniqKey="Curtis T">TP Curtis</name></author><author><name sortKey="Davenport, Rj" uniqKey="Davenport R">RJ Davenport</name></author><author><name sortKey="Hall, N" uniqKey="Hall N">N Hall</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kanagawa, T" uniqKey="Kanagawa T">T Kanagawa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Johansen, Fe" uniqKey="Johansen F">FE Johansen</name></author><author><name sortKey="Pekna, M" uniqKey="Pekna M">M Pekna</name></author><author><name sortKey="Norderhaug, In" uniqKey="Norderhaug I">IN Norderhaug</name></author><author><name sortKey="Haneberg, B" uniqKey="Haneberg B">B Haneberg</name></author><author><name sortKey="Hietala, Ma" uniqKey="Hietala M">MA Hietala</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jensen, Lj" uniqKey="Jensen L">LJ Jensen</name></author><author><name sortKey="Kuhn, M" uniqKey="Kuhn M">M Kuhn</name></author><author><name sortKey="Stark, M" uniqKey="Stark M">M Stark</name></author><author><name sortKey="Chaffron, S" uniqKey="Chaffron S">S Chaffron</name></author><author><name sortKey="Creevey, C" uniqKey="Creevey C">C Creevey</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Australie</li><li>France</li><li>Suisse</li></country><region><li>Canton de Berne</li><li>Canton de Zurich</li><li>Hauts-de-France</li><li>Nord-Pas-de-Calais</li><li>Victoria (État)</li></region><settlement><li>Berne</li><li>Lille</li><li>Melbourne</li><li>Zurich</li></settlement><orgName><li>Université de Melbourne</li><li>Université de Zurich</li></orgName></list><tree><country name="Suisse"><region name="Canton de Zurich"><name sortKey="Endt, Kathrin" sort="Endt, Kathrin" uniqKey="Endt K" first="Kathrin" last="Endt">Kathrin Endt</name></region><name sortKey="Chaffron, Samuel" sort="Chaffron, Samuel" uniqKey="Chaffron S" first="Samuel" last="Chaffron">Samuel Chaffron</name><name sortKey="Hardt, Wolf Dietrich" sort="Hardt, Wolf Dietrich" uniqKey="Hardt W" first="Wolf-Dietrich" last="Hardt">Wolf-Dietrich Hardt</name><name sortKey="Heikenwalder, Mathias" sort="Heikenwalder, Mathias" uniqKey="Heikenwalder M" first="Mathias" last="Heikenwalder">Mathias Heikenwalder</name><name sortKey="Macpherson, Andrew J" sort="Macpherson, Andrew J" uniqKey="Macpherson A" first="Andrew J." last="Macpherson">Andrew J. Macpherson</name><name sortKey="Mueller, Andreas J" sort="Mueller, Andreas J" uniqKey="Mueller A" first="Andreas J." last="Mueller">Andreas J. Mueller</name><name sortKey="Slack, Emma" sort="Slack, Emma" uniqKey="Slack E" first="Emma" last="Slack">Emma Slack</name><name sortKey="Stecher, B Rbel" sort="Stecher, B Rbel" uniqKey="Stecher B" first="B Rbel" last="Stecher">B Rbel Stecher</name><name sortKey="Von Mering, Christian" sort="Von Mering, Christian" uniqKey="Von Mering C" first="Christian" last="Von Mering">Christian Von Mering</name></country><country name="France"><noRegion><name sortKey="Tchitchek, Nicolas" sort="Tchitchek, Nicolas" uniqKey="Tchitchek N" first="Nicolas" last="Tchitchek">Nicolas Tchitchek</name></noRegion><name sortKey="Benecke, Arndt" sort="Benecke, Arndt" uniqKey="Benecke A" first="Arndt" last="Benecke">Arndt Benecke</name><name sortKey="Sirard, Jean Claude" sort="Sirard, Jean Claude" uniqKey="Sirard J" first="Jean-Claude" last="Sirard">Jean-Claude Sirard</name><name sortKey="Van Maele, Laurye" sort="Van Maele, Laurye" uniqKey="Van Maele L" first="Laurye" last="Van Maele">Laurye Van Maele</name></country><country name="Australie"><region name="Victoria (État)"><name sortKey="Strugnell, Richard" sort="Strugnell, Richard" uniqKey="Strugnell R" first="Richard" last="Strugnell">Richard Strugnell</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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