Role of Inflammasomes in Host Defense against Citrobacter rodentium Infection

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 ho...

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Veröffentlicht in:The Journal of biological chemistry 2012-05, Vol.287 (20), p.16955-16964
Hauptverfasser: Liu, Zhiping, Zaki, Md. Hasan, Vogel, Peter, Gurung, Prajwal, Finlay, B. Brett, Deng, Wanyin, Lamkanfi, Mohamed, Kanneganti, Thirumala-Devi
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Sprache:eng
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Zusammenfassung: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. Citrobacter rodentium is an enteric bacterial pathogen of mouse intestinal tract. Mice lacking Nlrp3, Nlrc4, and caspase-1 are hypersusceptible to C. rodentium-induced gastrointestinal inflammation. The Nlrp3 and Nlrc4 inflammasomes play a critical role in host defense against enteric infection caused by C. rodentium. Our study establishes a critical role of inflammasomes in host defense against Citrobacter rodentium infection.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M112.358705