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Updated: May 23, 2026
The Citrobacter rodentium Mouse Model: Studying Pathogen and Host Contributions to Infectious Colitis
Published on: February 19, 2013
Role of inflammasomes in host defense against Citrobacter rodentium infection
Zhiping Liu1, Md Hasan Zaki, Peter Vogel
1Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
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.
Insights
The Nlrp3 and Nlrc4 inflammasomes, crucial for interleukin (IL)-1β and IL-18 production, are vital for controlling Citrobacter rodentium infections in mice. Their absence leads to severe gastrointestinal inflammation and increased bacterial load.
Area of Science:
- Immunology
- Microbiology
- Gastroenterology
Background:
- Citrobacter rodentium is a mouse enteric pathogen causing inflammation similar to human E. coli infections.
- Inflammasome signaling regulates host responses to pathogens, but its role in C. rodentium infection is unknown.
Purpose of the Study:
- To investigate the in vivo role of inflammasome signaling in host defense against Citrobacter rodentium.
Main Methods:
- Mice deficient in inflammasome components (Nlrp3, Nlrc4, caspase-1) were infected with C. rodentium.
- Interleukin (IL)-1β and IL-18 production was assessed in knockout and wild-type mice.
- Macrophages were infected in vitro to study inflammasome activation.
Main Results:
- Mice lacking Nlrp3, Nlrc4, and caspase-1 showed increased susceptibility to C. rodentium, with heightened inflammation and bacterial burdens.
- Defective IL-1β and IL-18 production in knockout mice correlated with exacerbated disease.
- C. rodentium activated the Nlrp3 inflammasome in macrophages independently of the type III secretion system.
Conclusions:
- Nlrp3 and Nlrc4 inflammasome-mediated production of IL-1β and IL-18 is critical for host defense against Citrobacter rodentium.
- This pathway is essential for controlling enteric bacterial infections and limiting gastrointestinal inflammation.
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