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Epithelium-intrinsic NAIP/NLRC4 inflammasome drives infected enterocyte expulsion to restrict Salmonella replication in the intestinal mucosa
Institute of Microbiology, ETH Zürich, 8093 Zürich, Switzerland.
Institute of Microbiology, ETH Zürich, 8093 Zürich, Switzerland.
Institute of Microbiology, ETH Zürich, 8093 Zürich, Switzerland.
Institute of Microbiology, ETH Zürich, 8093 Zürich, Switzerland.
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2014 (English)In: Cell Host and Microbe, ISSN 1931-3128, E-ISSN 1934-6069, Vol. 16, no 2, p. 237-248Article in journal (Refereed) Published
Abstract [en]

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 ∼100-fold higher intraepithelial loads and accelerated lymph node colonization. Interestingly, the cytokines downstream of inflammasome activation, interleukin (IL)-1α/β 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.

Place, publisher, year, edition, pages
2014. Vol. 16, no 2, p. 237-248
National Category
Infectious Medicine Microbiology in the medical area
Identifiers
URN: urn:nbn:se:uu:diva-309867DOI: 10.1016/j.chom.2014.07.001ISI: 000341144100013PubMedID: 25121751OAI: oai:DiVA.org:uu-309867DiVA, id: diva2:1053045
Funder
Swedish Research Council, 2012-262Available from: 2016-12-08 Created: 2016-12-08 Last updated: 2018-01-13Bibliographically approved

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Sellin, Mikael E.

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