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Publication : Role of inflammasomes in host defense against Citrobacter rodentium infection.

First Author  Liu Z Year  2012
Journal  J Biol Chem Volume  287
Issue  20 Pages  16955-64
PubMed ID  22461621 Mgi Jnum  J:185438
Mgi Id  MGI:5428789 Doi  10.1074/jbc.M112.358705
Citation  Liu Z, et al. (2012) Role of inflammasomes in host defense against Citrobacter rodentium infection. J Biol Chem 287(20):16955-64
abstractText  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)-1beta and IL-18 production given that il-1beta(-/-) 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-1beta and IL-18 downstream of the Nlrp3 and Nlrc4 inflammasomes plays a critical role in host defense against enteric infections caused by C. rodentium.
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