The microbiota mediates pathogen clearance from the gut lumen after non-typhoidal Salmonella diarrhea.

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 S. typhimurium diarrhea. This pathogen is a common cau...

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Autores principales:	Kathrin Endt, Bärbel Stecher, Samuel Chaffron, Emma Slack, Nicolas Tchitchek, Arndt Benecke, Laurye Van Maele, Jean-Claude Sirard, Andreas J Mueller, Mathias Heikenwalder, Andrew J Macpherson, Richard Strugnell, Christian von Mering, Wolf-Dietrich Hardt
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/29b94b6f467d4775af5bc84134f426d3
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spelling	oai:doaj.org-article:29b94b6f467d4775af5bc84134f426d32021-11-18T06:01:38ZThe microbiota mediates pathogen clearance from the gut lumen after non-typhoidal Salmonella diarrhea.1553-73661553-737410.1371/journal.ppat.1001097https://doaj.org/article/29b94b6f467d4775af5bc84134f426d32010-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20844578/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Many 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 S. typhimurium diarrhea. This pathogen is a common cause of diarrhea in humans world-wide. S. typhimurium (S. tm(att), sseD) 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 S. typhimurium O-antigen (wbaP, S. enteritidis) and sIgA-deficient mice (TCRβ(-/-)δ(-/-), J(H) (-/-), IgA(-/-), pIgR(-/-)). 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 S. tm(att) 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 S. typhimurium diarrhea and for preventing transmission.Kathrin EndtBärbel StecherSamuel ChaffronEmma SlackNicolas TchitchekArndt BeneckeLaurye Van MaeleJean-Claude SirardAndreas J MuellerMathias HeikenwalderAndrew J MacphersonRichard StrugnellChristian von MeringWolf-Dietrich HardtPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 6, Iss 9, p e1001097 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Kathrin Endt Bärbel Stecher Samuel Chaffron Emma Slack Nicolas Tchitchek Arndt Benecke Laurye Van Maele Jean-Claude Sirard Andreas J Mueller Mathias Heikenwalder Andrew J Macpherson Richard Strugnell Christian von Mering Wolf-Dietrich Hardt The microbiota mediates pathogen clearance from the gut lumen after non-typhoidal Salmonella diarrhea.
description	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 S. typhimurium diarrhea. This pathogen is a common cause of diarrhea in humans world-wide. S. typhimurium (S. tm(att), sseD) 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 S. typhimurium O-antigen (wbaP, S. enteritidis) and sIgA-deficient mice (TCRβ(-/-)δ(-/-), J(H) (-/-), IgA(-/-), pIgR(-/-)). 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 S. tm(att) 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 S. typhimurium diarrhea and for preventing transmission.
format	article
author	Kathrin Endt Bärbel Stecher Samuel Chaffron Emma Slack Nicolas Tchitchek Arndt Benecke Laurye Van Maele Jean-Claude Sirard Andreas J Mueller Mathias Heikenwalder Andrew J Macpherson Richard Strugnell Christian von Mering Wolf-Dietrich Hardt
author_facet	Kathrin Endt Bärbel Stecher Samuel Chaffron Emma Slack Nicolas Tchitchek Arndt Benecke Laurye Van Maele Jean-Claude Sirard Andreas J Mueller Mathias Heikenwalder Andrew J Macpherson Richard Strugnell Christian von Mering Wolf-Dietrich Hardt
author_sort	Kathrin Endt
title	The microbiota mediates pathogen clearance from the gut lumen after non-typhoidal Salmonella diarrhea.
title_short	The microbiota mediates pathogen clearance from the gut lumen after non-typhoidal Salmonella diarrhea.
title_full	The microbiota mediates pathogen clearance from the gut lumen after non-typhoidal Salmonella diarrhea.
title_fullStr	The microbiota mediates pathogen clearance from the gut lumen after non-typhoidal Salmonella diarrhea.
title_full_unstemmed	The microbiota mediates pathogen clearance from the gut lumen after non-typhoidal Salmonella diarrhea.
title_sort	microbiota mediates pathogen clearance from the gut lumen after non-typhoidal salmonella diarrhea.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/29b94b6f467d4775af5bc84134f426d3
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The microbiota mediates pathogen clearance from the gut lumen after non-typhoidal Salmonella diarrhea.

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