Journal
CELL HOST & MICROBE
Volume 16, Issue 2, Pages 237-248Publisher
CELL PRESS
DOI: 10.1016/j.chom.2014.07.001
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Funding
- Swiss National Foundation grants (SNF) [310030_132997, 310030_53074, CRSII3_136286]
- Swedish Research Council international postdoc fellowship [2012-262]
- EMBO long-term fellowship (ALTF) [1227-2010]
- Australian overseas postdoctoral fellowship [APP1013515]
- Institute for Arthritis Research Lausanne
- ScopeM
- RCHCI of ETHZ
- Swiss National Science Foundation (SNF) [310030_132997, CRSII3_136286] Funding Source: Swiss National Science Foundation (SNF)
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The gut mucosal epithelium separates the host from the microbiota, but enteropathogens such as Salmonella Typhimurium (S.Tm) can invade and breach this barrier. Defenses against such acute insults remain incompletely understood. Using a murine model of Salmonella enterocolitis, we analyzed mechanisms limiting pathogen loads in the epithelium during early infection. Although the epithelium-invading S.Tm replicate initially, this intraepithelial replicative niche is restricted by expulsion of infected enterocytes into the lumen. This mechanism is compromised if inflammasome components (NAIP1-6, NLRC4, caspase-1/-11) are deleted, or ablated specifically in the epithelium, resulting in similar to 100-fold higher intraepithelial loads and accelerated lymph node colonization. Interestingly, the cytokines downstream of inflammasome activation, interleukin (IL)-1 alpha/beta and IL-18, appear dispensable for epithelial restriction of early infection. These data establish the role of an epithelium-intrinsic inflammasome, which drives expulsion of infected cells to restrict the pathogen's intraepithelial proliferation. This may represent a general defense mechanism against mucosal infections.
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