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

• Published in: Immunobiology (1979) Vol. 217; no. 8; pp. 795 - 807
• Main Authors: Rojas-López, A.E, Soldevila, G, Meza-Pérez, S, DuPont, G, Ostoa-Saloma, P, Wurbel, M.A, Ventura-Juárez, J, Flores-Romo, L, García-Zepeda, E.A
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier GmbH 01-08-2012
• Subjects: Advanced Basic Science; Allergy and Immunology; Amoebiasis; Animals; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Chemokine CCL11 - genetics; Chemokine CCL11 - immunology; Chemokine CCL11 - metabolism; Chemokine CCL20 - genetics; Chemokine CCL20 - immunology; Chemokine CCL20 - metabolism; Chemokine receptor; Chemokines; Chemokines, CC - genetics; Chemokines, CC - immunology; Chemokines, CC - metabolism; Colitis; Disease Models, Animal; Dysentery, Amebic - immunology; Dysentery, Amebic - metabolism; Dysentery, Amebic - parasitology; Entamoeba histolytica; Entamoeba histolytica - immunology; Entamoeba histolytica - physiology; Flow Cytometry; Forkhead Transcription Factors - immunology; Forkhead Transcription Factors - metabolism; Gene Expression; Humans; Inflammation; Inflammation Mediators - immunology; Inflammation Mediators - metabolism; Interferon-gamma - immunology; Interferon-gamma - metabolism; Interleukin-17 - immunology; Interleukin-17 - metabolism; Interleukin-2 Receptor alpha Subunit - immunology; Interleukin-2 Receptor alpha Subunit - metabolism; Interleukin-4 - immunology; Interleukin-4 - metabolism; Interleukin-6 - immunology; Interleukin-6 - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, CCR - genetics; Receptors, CCR - immunology; Receptors, CCR - metabolism; Regulatory T cells; Reverse Transcriptase Polymerase Chain Reaction; Trophozoites - immunology; Trophozoites - physiology; Tumor Necrosis Factor-alpha - immunology; Tumor Necrosis Factor-alpha - metabolism; intra epithelial cells; quantitative real time-polymerase chain reaction; CAC; KO; LP; qRT-PCR; Treg; Entamoeba histolytica; Chemokine receptor; Inflammation; MLN; chronic amoebic colitis; regulatory T cells; fetal bovine serum; IEL; knock out; mesentheric lymph nodes; Amoebiasis; FBS; lamina propria; wild type; Colitis; WT; Chemokines; Regulatory T cells
• ISSN: 0171-2985; 1878-3279
• DOI: 10.1016/j.imbio.2012.04.005

Abstract 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.