CCR9p>+p> T cells contribute to the resolution of the inflammatory response in a mouse model of intestinal amoebiasis

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• 作者：A.E. Rojas-Ló ; pezp>ap>p> ; p>p>bp> ; G. Soldevilap>bp> ; S. Meza-Pé ; rezp>cp> ; G. DuPontp>ap>p> ; p>p>bp> ; P. Ostoa-Salomap>bp> ; M.A. Wurbelp>dp> ; J. Ventura-Juá ; rezp>ep> ; L. Flores-Romop>cp> ; E.A. Garcí ; a-Zepedap>ap>p> ; p>p>bp>p> ; p>p>garciaze@servidor.unam.mxp>p> ; p>p>garciaze@biomedicas.unam.mxp>
• 关键词：CAC ; chronic amoebic colitis ; FBS ; fetal bovine serum ; IEL ; intra epithelial cells ; KO ; knock out ; LP ; lamina propria ; MLN ; mesentheric lymph nodes ; qRT-PCR ; quantitative real time-polymerase chain reaction ; Treg ; regulatory T cells ; WT ; wild type
• 刊名：Immunobiology
• 出版年：2012
• 期刊代码：3_01712985
• 类别：imm
• 出版时间：August, 2012
• 卷：217
• 期：8
• 页码：795-807
• 文件大小：2023 K

摘要

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 (CCR9p>鈭?鈭?/sup>) mice to investigate the role of the CCR9p>+p> T cells in a murine model of E. histolytica intestinal infection. Intracecal infection of CCR9p>+/+p>, CCR9p>+/鈭?/sup> and CCR9p>鈭?鈭?/sup> mice with E. histolytica trophozoites, revealed striking differences in the development and nature of the intestinal inflammatory response observed between these strains. While CCR9p>+/+p> and CCR9p>+/鈭?/sup> mice were resistant to the infection and resolved the pathogen-induced inflammatory response, CCR9p>鈭?鈭?/sup> mice developed a chronic inflammatory response, which was associated with over-expression of the cytokines IFN-纬, TNF-伪, 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 CCR9p>鈭?鈭?/sup> mice. E. histolytica trophozoites were identified in the lumen of the cecum of CCR9p>鈭?鈭?/sup> mice at seven days post infection (pi), whereas in CCR9p>+/+p> mice trophozoites disappeared by day 1 pi. Interestingly, the inflammation observed in CCR9p>鈭?鈭?/sup> mice, was associated with a delayed recruitment of CD4p>+p>CD25p>+p>FoxP3p>+p> 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, CCR9p>+p> T cells were also identified in colon tissue sections obtained from patients with amoebic colitis. Our data suggest that a population of CCR9p>+p>CD4p>+p>CD25p>+p>FoxP3p>+p> T cells may participate in the control and resolution of the inflammatory immune response to E. histolytica infection.