Role of inflammasomes in host defense against citrobacter rodentium infection

Zhiping Liu, Md Hasan Zaki, Peter Vogel, Prajwal Gurung, B. Brett Finlay, Wanyin Deng, Mohamed Lamkanfi, Thirumala Devi Kanneganti

Research output: Contribution to journalArticle

89 Scopus citations

Abstract

Citrobacter rodentium is an enteric bacterial pathogen of the mouse intestinal tract that triggers inflammatory responses resembling those of humans infected with enteropathogenic and enterohemorrhagic Escherichia coli. Inflammasome signaling is emerging as a central regulator of inflammatory and host responses to several pathogens, but the in vivo role of inflammasome signaling in host defense against C. rodentium has not been characterized. Here, we show that mice lacking the inflammasome components Nlrp3, Nlrc4, and caspase-1 were hypersusceptible to C. rodentium-induced gastrointestinal inflammation. This was due to defective interleukin (IL)-1β and IL-18 production given that il-1β-/- and il-18-/- mice also suffered from increased bacterial burdens and exacerbated histopathology. C. rodentium specifically activated the Nlrp3 inflammasome in in vitro-infected macrophages independently of a functional bacterial type III secretion system. Thus, production of IL-1β and IL-18 downstream of the Nlrp3 and Nlrc4 inflammasomes plays a critical role in host defense against enteric infections caused by C. rodentium.

Original languageEnglish (US)
Pages (from-to)16955-16964
Number of pages10
JournalJournal of Biological Chemistry
Volume287
Issue number20
DOIs
StatePublished - May 11 2012

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Liu, Z., Zaki, M. H., Vogel, P., Gurung, P., Finlay, B. B., Deng, W., Lamkanfi, M., & Kanneganti, T. D. (2012). Role of inflammasomes in host defense against citrobacter rodentium infection. Journal of Biological Chemistry, 287(20), 16955-16964. https://doi.org/10.1074/jbc.M112.358705