Mucosal-associated invariant T (MAIT) cells are innate-like T cells mainly found in the mucosa and peripheral blood. We have recently demonstrated that Clostridioides difficile activates MAIT cells in vitro. However, their role in the pathogenesis of C. difficile infection (CDI) in human patients remains elusive to date. In this study, we performed comprehensive immunophenotyping of MAIT cells derived from CDI patients and compared their phenotype to that of patients with inflammatory bowel diseases (IBD) and healthy controls. Our study revealed that blood MAIT cells from CDI patients exhibit an interleukin 17a (IL-17a)-dominated proinflammatory phenotype and an increased readiness to synthesize the proinflammatory cytokine interferon γ (IFN-γ) following in vitro re-stimulation. Moreover, the cytotoxic activity of MAIT cells, as measured by surface CD107a and intracellular granzyme B expression, was strongly increased in CDI. Multi epitope ligand cartography (MELC) analysis of intestinal biopsies from CDI patients revealed that MAIT cells exhibit an increased production of granzyme B and increased cytotoxicity compared to the control group. Together with previously published in vitro data from our group, our findings suggest that MAIT cells are functionally involved in the immune response against C. difficile and contribute to the pathogenesis of CDI.

中文翻译：

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来自艰难梭菌感染患者的粘膜相关不变 T 细胞表现出独特的促炎表型和增强的细胞毒活性。

粘膜相关不变T细胞（MAIT）是先天性T细胞，主要存在于粘膜和外周血中。我们最近证明艰难梭菌可以在体外激活 MAIT 细胞。然而，迄今为止，它们在人类患者艰难梭菌感染（CDI）发病机制中的作用仍然难以捉摸。在这项研究中，我们对 CDI 患者的 MAIT 细胞进行了全面的免疫表型分析，并将其表型与炎症性肠病 (IBD) 患者和健康对照的表型进行了比较。我们的研究表明，CDI 患者的血液 MAIT 细胞表现出以白细胞介素 17a (IL-17a) 为主的促炎表型，并且在体外再刺激后合成促炎细胞因子干扰素 γ (IFN-γ) 的准备度增加。此外，通过表面 CD107a 和细胞内颗粒酶 B 表达测量，MAIT 细胞的细胞毒活性在 CDI 中显着增加。对 CDI 患者肠道活检的多表位配体制图 (MELC) 分析显示，与对照组相比，MAIT 细胞的颗粒酶 B 产量增加，细胞毒性增加。结合我们小组之前发表的体外数据，我们的研究结果表明，MAIT 细胞在功能上参与针对艰难梭菌的免疫反应，并有助于 CDI 的发病机制。