Elsevier

Mucosal Immunology

Volume 7, Issue 4, July 2014, Pages 763-774
Mucosal Immunology

Article
Nlrp3 activation in the intestinal epithelium protects against a mucosal pathogen

https://doi.org/10.1038/mi.2013.94Get rights and content
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Abstract

Polymorphisms in the intracellular pattern recognition receptor gene NLRP3 (NLR family, pyrin domain containing 3) have been associated with susceptibility to Crohn's disease, a type of inflammatory bowel disease. Following tissue damage or infection, NLRP3 triggers the formation of inflammasomes, containing NLRP3, ASC (apoptosis-associated speck-like protein containing a CARD domain), and caspase-1, that mediate secretion of interleukin (IL)-1β and IL-18. However, the precise role of NLRP3 inflammasomes in mucosal inflammation and barrier protection remains unclear. Here we show that upon infection with the attaching/effacing intestinal pathogen Citrobacter rodentium, Nlrp3−/− and Asc−/− mice displayed increased bacterial colonization and dispersion, more severe weight loss, and exacerbated intestinal inflammation. Analyses of irradiation bone marrow chimeras revealed that protection from disease was mediated through Nlrp3 activation in nonhematopoietic cells and was initiated very early after infection. Thus, early activation of Nlrp3 in intestinal epithelial cells limits pathogen colonization and prevents subsequent pathology, potentially providing a functional link between NLRP3 polymorphisms and susceptibility to inflammatory bowel disease.

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Published online: 27 November 2013

SUPPLEMENTARY MATERIAL is linked to the online version of the paper

G X Song-Zhao and N Srinivasan: These authors contributed equally to this work.

Supplementary information The online version of this article (doi:10.1038/mi.2013.94) contains supplementary material, which is available to authorized users.