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

doi:10.1074/jbc.M112.358705

Back

Role of Inflammasomes in Host Defense against Citrobacter rodentium Infection

Journal article

Open access

Peer reviewed

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 and Thirumala-Devi Kanneganti

The Journal of biological chemistry, Vol.287(20), pp.16955-16964

05/11/2012

DOI: 10.1074/jbc.M112.358705

PMCID: PMC3351318

PMID: 22461621

Files and links (1)

url

https://doi.org/10.1074/jbc.M112.358705View

Published (Version of record) Open Access

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. 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.

Host-Pathogen Interactions

Immunology

Innate Immunity

Inflammation

Inflammasome

Colitis

Citrobacter rodentium

Details

Title: Subtitle: Role of Inflammasomes in Host Defense against Citrobacter rodentium Infection
Creators: Zhiping Liu - Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105
Md. Hasan Zaki - Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105
Peter Vogel - Animal Resources Center and the Veterinary Pathology Core, St. Jude Children's Research Hospital, Memphis, Tennessee 38105
Prajwal Gurung - Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105
B. Brett Finlay - Michael Smith Laboratories, the University of British Columbia, Vancouver British Columbia V6T 1Z4, Canada
Wanyin Deng - Michael Smith Laboratories, the University of British Columbia, Vancouver British Columbia V6T 1Z4, Canada
Mohamed Lamkanfi - Departments of Biochemistry and Ghent University,VIB, B-9000 Ghent, Belgium
Thirumala-Devi Kanneganti - Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.287(20), pp.16955-16964
DOI: 10.1074/jbc.M112.358705
PMID: 22461621
PMCID: PMC3351318
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: Elsevier Inc
Grant note: R01AR056296 / National Institutes of Health
Language: English
Date published: 05/11/2012
Academic Unit: Infectious Diseases; Internal Medicine
Record Identifier: 9984094521702771

Metrics

13 Record Views

129 Times Cited - Web of Science