Role of Inflammasomes in Host Defense against Citrobacter rodentium Infection

被引：123

作者：

Liu, Zhiping ^{[1
]}

Zaki, Md Hasan ^{[1
]}

Vogel, Peter ^{[2
]}

Gurung, Prajwal ^{[1
]}

Finlay, B. Brett ^{[3
,4
]}

Deng, Wanyin ^{[3
,4
]}

Lamkanfi, Mohamed ^{[5
]}

Kanneganti, Thirumala-Devi ^{[1
]}

机构：

[1] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA

[2] St Jude Childrens Res Hosp, Anim Resources Ctr, Memphis, TN 38105 USA

[3] Univ British Columbia, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada

[4] Ghent Univ VIB, Dept Biochem, B-9000 Ghent, Belgium

[5] Ghent Univ VIB, Dept Med Prot Res, B-9000 Ghent, Belgium

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2012年 / 287卷 / 20期

基金：

美国国家卫生研究院;

关键词：

EFFACING PATHOGEN; INDUCED COLITIS; MICE DEFICIENT; DISEASE; INTERLEUKIN-1-BETA; ACTIVATION; CASPASE-1; SECRETION; VIRULENCE; MYD88;

D O I：

10.1074/jbc.M112.358705

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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)-1 beta and IL-18 production given that il-1 beta(-/-) 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-1 beta and IL-18 downstream of the Nlrp3 and Nlrc4 inflammasomes plays a critical role in host defense against enteric infections caused by C. rodentium.

引用

页码：16955 / 16964

页数：10

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