Tight junctional disruption and apoptosis in an in vitro model of Citrobacter rodentium infection
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Updated: Jul 5, 2026
The Citrobacter rodentium Mouse Model: Studying Pathogen and Host Contributions to Infectious Colitis
Published on: February 19, 2013
Andrew N Flynn1, Andre G Buret
1Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada.
Abstract:
The murine model of Citrobacter rodentium infection has been used to complement in vitro studies of enteropathogenic Escherichia coli (EPEC) infections of human intestinal epithelial cells (IECs). However, the differences in epithelial cell responses between these two models are not fully understood. We used an in vitro model of C. rodentium infection to examine important, yet incompletely understood, cellular responses of murine IECs to this pathogen. C. rodentium attached to CMT-93 cells and disrupted their tight junctional expression of claudins-4 and -5. This was associated with a loss of barrier function that required live bacteria and was partially prevented by the inhibition of Rho kinase. Furthermore, C. rodentium caused an upregulation of IEC apoptosis that was associated with the cytoplasmic accumulation of apoptosis-inducing factor, but not with the activation of caspase-3. These studies demonstrate for the first time that C. rodentium affects murine IECs in ways that may be similar, but distinct, to the effects of EPEC on human IECs.
Insights
Citrobacter rodentium infection disrupts murine intestinal epithelial cell barrier function and induces apoptosis. These effects differ from enteropathogenic E. coli in human cells, highlighting distinct host-pathogen interactions.
Area of Science:
- Microbiology
- Cell Biology
- Immunology
Background:
- The murine Citrobacter rodentium infection model complements in vitro studies of human enteropathogenic E. coli (EPEC) infections.
- Understanding differences in epithelial cell responses between these models is crucial for infectious disease research.
Purpose of the Study:
- To investigate cellular responses of murine intestinal epithelial cells (IECs) to C. rodentium infection in vitro.
- To elucidate the mechanisms underlying C. rodentium-induced disruption of IECs.
Main Methods:
- Infection of CMT-93 murine intestinal epithelial cells with C. rodentium.
- Assessment of tight junction protein expression (claudins-4, -5) and barrier function.
- Evaluation of apoptosis markers, including apoptosis-inducing factor and caspase-3 activation.
- Inhibition studies using Rho kinase inhibitors.
Main Results:
- C. rodentium attachment disrupted claudin-4 and -5 expression, leading to loss of barrier function.
- Barrier function loss required live bacteria and was partially mediated by Rho kinase.
- C. rodentium induced IEC apoptosis via apoptosis-inducing factor accumulation, independent of caspase-3 activation.
Conclusions:
- C. rodentium induces distinct cellular responses in murine IECs compared to EPEC in human IECs.
- The study reveals novel insights into C. rodentium pathogenesis and host-pathogen interactions at the cellular level.
