24:T537,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.25:T4bc,Inflammatory diseases of the gastrointestinal tract are emerging as a global problem with increased evidence and prevalence in numerous countries. A dysregulated sphingolipid metabolism occurs in patients with ulcerative colitis and is discussed to contribute to its pathogenesis. In the present study, we determined the impact of acid sphingomyelinase (Asm), which catalyzes the hydrolysis of sphingomyelin to ceramide, on the course of Citrobacter (C.) rodentium-driven colitis. C. rodentium is an enteric pathogen and induces colonic inflammation very similar to the pathology in patients with ulcerative colitis. We found that mice with Asm deficiency or Asm inhibition were strongly susceptible to C. rodentium infection. These mice showed increased levels of C. rodentium in the feces and were prone to bacterial spreading to the systemic organs. In addition, mice lacking Asm activity showed an uncontrolled inflammatory T_h1 and T_h17 response, which was accompanied by a stronger colonic pathology compared to infected wild type mice. These findings identified Asm as an essential regulator of mucosal immunity to the enteric pathogen C. rodentium.

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