TY - JOUR
T1 - Role of inflammasomes in host defense against citrobacter rodentium infection
AU - Liu, Zhiping
AU - Zaki, Md Hasan
AU - Vogel, Peter
AU - Gurung, Prajwal
AU - Finlay, B. Brett
AU - Deng, Wanyin
AU - Lamkanfi, Mohamed
AU - Kanneganti, Thirumala Devi
PY - 2012/5/11
Y1 - 2012/5/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84860859210&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84860859210&partnerID=8YFLogxK
U2 - 10.1074/jbc.M112.358705
DO - 10.1074/jbc.M112.358705
M3 - Article
C2 - 22461621
AN - SCOPUS:84860859210
SN - 0021-9258
VL - 287
SP - 16955
EP - 16964
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 20
ER -