Nlrp3 activation in the intestinal epithelium protects against a mucosal pathogen

Song-Zhao, G.X., Srinivasan, N., Pott, J., Baban, D., Frankel, G. and Maloy, K.J. (2014) Nlrp3 activation in the intestinal epithelium protects against a mucosal pathogen. Mucosal Immunology, 7, pp. 763-774. (doi: 10.1038/mi.2013.94) (PMID:24280937) (PMCID:PMC4048180)

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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.

Item Type:Articles
Additional Information:This work was supported by grants from the Wellcome Trust (to K.J.M. and G.F.), a MSD-Norman Heatley Studentship ( to G.X.S.-Z.), the Clarendon Fund (to G.X.S.-Z. and N.S.), and an EMBO fellowship (to J.P.).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Maloy, Professor Kevin
Authors: Song-Zhao, G.X., Srinivasan, N., Pott, J., Baban, D., Frankel, G., and Maloy, K.J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Mucosal Immunology
Publisher:Springer Nature
ISSN:1933-0219
ISSN (Online):1935-3456
Published Online:27 November 2013

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