CCR9+ T cells contribute to the resolution of the inflammatory response in a mouse model of intestinal amoebiasis

Analysis of the mechanisms underlying the inflammatory response in amoebiasis is important to understand the immunopathology of the disease. Mucosal associated effector and regulatory T cells may play a role in regulating the inflammatory immune response associated to Entamoeba histolytica infection in the colon. A subpopulation of regulatory T cells has recently been identified and is characterized by the expression of the chemokine receptor CCR9. In this report, we used CCR9 deficient (CCR9−/−) mice to investigate the role of the CCR9+ T cells in a murine model of E. histolytica intestinal infection. Intracecal infection of CCR9+/+, CCR9+/− and CCR9−/− mice with E. histolytica trophozoites, revealed striking differences in the development and nature of the intestinal inflammatory response observed between these strains. While CCR9+/+ and CCR9+/− mice were resistant to the infection and resolved the pathogen-induced inflammatory response, CCR9−/− mice developed a chronic inflammatory response, which was associated with over-expression of the cytokines IFN-γ, TNF-α, IL-4, IL-6 and IL-17, while IL-10 was not present. In addition, increased levels of CCL11, CCL20 and CCL28 chemokines were detected by qRT-PCR in CCR9−/− mice. E. histolytica trophozoites were identified in the lumen of the cecum of CCR9−/− mice at seven days post infection (pi), whereas in CCR9+/+ mice trophozoites disappeared by day 1 pi. Interestingly, the inflammation observed in CCR9−/− mice, was associated with a delayed recruitment of CD4+CD25+FoxP3+ T cells to the cecal epithelium and lamina propria, suggesting that this population may play a role in the early regulation of the inflammatory response against E. histolytica, likely through IL-10 production. In support of these data, CCR9+ T cells were also identified in colon tissue sections obtained from patients with amoebic colitis. Our data suggest that a population of CCR9+CD4+CD25+FoxP3+ T cells may participate in the control and resolution of the inflammatory immune response to E. histolytica infection.