Salmonella enterica serovar typhimurium exploits inflammation to compete with the intestinal microbiota

被引:821
作者
Stecher, Baerbel
Robbiani, Riccardo
Walker, Alan W.
Westendorf, Astrid M.
Barthel, Manja
Kremer, Marcus
Chaffron, Samuel
Macpherson, Andrew J.
Buer, Jan
Parkhill, Julian
Dougan, Gordon
von Mering, Christian
Hardt, Wolf-Dietrich [1 ]
机构
[1] Swiss Inst Technol Zurich, Inst Microbiol, Zurich, Switzerland
[2] Wellcome Trust Sanger Inst, Cambridge, England
[3] Helmholtz Ctr Infect Res, Dept Mucosal Immun, Braunschweig, Germany
[4] Tech Univ Munich, D-8000 Munich, Germany
[5] Univ Zurich, Inst Mol Biol, Bioinformat Grp, Zurich, Switzerland
[6] McMaster Univ, Fac Hlth Sci, Hamilton, ON, Canada
基金
英国惠康基金;
关键词
D O I
10.1371/journal.pbio.0050244
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Most mucosal surfaces of the mammalian body are colonized by microbial communities ("microbiota''). A high density of commensal microbiota inhabits the intestine and shields from infection ("colonization resistance''). The virulence strategies allowing enteropathogenic bacteria to successfully compete with the microbiota and overcome colonization resistance are poorly understood. Here, we investigated manipulation of the intestinal microbiota by the enteropathogenic bacterium Salmonella enterica subspecies 1 serovar Typhimurium (S. Tm) in a mouse colitis model: we found that inflammatory host responses induced by S. Tm changed microbiota composition and suppressed its growth. In contrast to wild-type S. Tm, an avirulent invGsseD mutant failing to trigger colitis was outcompeted by the microbiota. This competitive defect was reverted if inflammation was provided concomitantly by mixed infection with wild-type S. Tm or in mice (IL10-/-, VILLIN-HA(CL4-CD8)) with inflammatory bowel disease. Thus, inflammation is necessary and sufficient for overcoming colonization resistance. This reveals a new concept in infectious disease: in contrast to current thinking, inflammation is not always detrimental for the pathogen. Triggering the host's immune defence can shift the balance between the protective microbiota and the pathogen in favour of the pathogen.
引用
收藏
页码:2177 / 2189
页数:13
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