CEACAM1 regulates CD8⁺ T cell immunity and protects from severe pathology during Citrobacter rodentium induced colitis

ABSTRACT

The incidence of gastrointestinal infections continues to increase, and infectious colitis contributes significantly to morbidity and mortality worldwide. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) has been discovered to be strongly involved in the intestinal homeostasis. However, whether intestinal CEACAM1 expression has an impact on the control of infectious colitis remains elusive. Citrobacter rodentium (C. rodentium) is a gram-negative enteric pathogen that induces colonic inflammation in mice, with a critical role for CD4⁺ T cell but not CD8⁺ T cell immunity to primary infection. Here, we show that Ceacam1^−/− mice are much more susceptible to C. rodentium infection than wildtype mice, which is mediated by a defect in the intestinal barrier and, surprisingly, by a dysregulated CD8⁺ T cell but not CD4⁺ T cell response in the colon. CEACAM1 expression is essential for the control of CD8⁺ T cell immunity, as CEACAM1 deficiency during C. rodentium infection inhibits CD8⁺ T cell exhaustion. We conclude that CEACAM1 is an important regulator of CD8⁺ T cell function in the colon, and blocking CEACAM1 signaling to activate CD8⁺ T cells may have unforeseen side effects.

KEYWORDS:

• CEACAM1
• enteric infection
• infectious colitis
• CD8 T cells
• inhibitory molecule

Acknowledgments

We kindly thank Mechthild Hemmler-Roloff and Patrick Juszczak for excellent technical assistance. We are thankful to Daniela Catrini for the critical reading of the manuscript. This work was supported by the Deutsche Forschungsgemeinschaft (DFG –RTG 1949 and RTG 2098).

Disclosure of Potential Conflicts of Interest

The authors report no conflict of interest.

Additional information

Funding

This work was supported by the Deutsche Forschungsgemeinschaft [RTG2098, RTG1949].