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The microbiota mediates pathogen clearance from the gut lumen after non-typhoidal salmonella diarrhea
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نویسنده
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endt k. ,stecher b. ,chaffron s. ,slack e. ,tchitchek n. ,benecke a. ,van maele l. ,sirard j.-c. ,mueller a.j. ,heikenwalder m. ,macpherson a.j. ,strugnell r. ,von mering c. ,hardt w.-d.
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منبع
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plos pathogens - 2010 - دوره : 6 - شماره : 9
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چکیده
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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. tmatt,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-/-,jh-/-,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. tmatt 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. © 2010 endt et al.
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آدرس
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institute of microbiology,eth zürich,zürich, Switzerland, institute of microbiology,eth zürich,zürich, Switzerland, institute of molecular biology and swiss institute of bioinformatics,university of zürich,zürich, Switzerland, gastroenterology inselspital,department klinische forschung,bern, Switzerland, institut des hautes études scientifiques and cnrs usr3078,bures sur yvette, France, institut des hautes études scientifiques and cnrs usr3078,bures sur yvette, France, institut national de la santé et de la recherche médicale,u801,france,institut pasteur de lille,univ. lille nord de france,udsl,lille, France, institut national de la santé et de la recherche médicale,u801,france,institut pasteur de lille,univ. lille nord de france,udsl,lille, France, institute of microbiology,eth zürich,zürich, Switzerland, institute of neuropathology,university hospital of zurich,zürich, Switzerland, gastroenterology inselspital,department klinische forschung,bern, Switzerland, department of microbiology and immunology,the university of melbourne,parkville,vic, Australia, institute of molecular biology and swiss institute of bioinformatics,university of zürich,zürich, Switzerland, institute of microbiology,eth zürich,zürich, Switzerland
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Authors
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