Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria 3000, Australia.
Centre for Animal Biotechnology, Faculty of Veterinary and Agricultural Sciences,The University of Melbourne, Victoria 3010, Australia.
J Immunol. 2018 Mar 1;200(5):1901-1916. doi: 10.4049/jimmunol.1701512. Epub 2018 Jan 29.
Mucosal-associated invariant T (MAIT) cells produce inflammatory cytokines and cytotoxic granzymes in response to by-products of microbial riboflavin synthesis. Although MAIT cells are protective against some pathogens, we reasoned that they might contribute to pathology in chronic bacterial infection. We observed MAIT cells in proximity to bacteria in human gastric tissue, and so, using MR1-tetramers, we examined whether MAIT cells contribute to chronic gastritis in a mouse SS1 infection model. Following infection, MAIT cells accumulated to high numbers in the gastric mucosa of wild-type C57BL/6 mice, and this was even more pronounced in MAIT TCR transgenic mice or in C57BL/6 mice where MAIT cells were preprimed by Ag exposure or prior infection. Gastric MAIT cells possessed an effector memory Tc1/Tc17 phenotype, and were associated with accelerated gastritis characterized by augmented recruitment of neutrophils, macrophages, dendritic cells, eosinophils, and non-MAIT T cells and by marked gastric atrophy. Similarly treated MR1 mice, which lack MAIT cells, showed significantly less gastric pathology. Thus, we demonstrate the pathogenic potential of MAIT cells in -associated immunopathology, with implications for other chronic bacterial infections.
黏膜相关不变 T（MAIT）细胞在受到微生物核黄素合成副产物的刺激后会产生炎症细胞因子和细胞毒性颗粒酶。尽管 MAIT 细胞对某些病原体具有保护作用，但我们认为它们可能会导致慢性细菌感染的病理变化。我们观察到人类胃组织中的 MAIT 细胞与细菌相邻，因此，我们使用 MR1-四聚体检查 MAIT 细胞是否会在 SS1 感染的小鼠模型中导致慢性胃炎。感染后，MAIT 细胞在野生型 C57BL/6 小鼠的胃黏膜中大量积聚，而在 MAIT TCR 转基因小鼠或在 MAIT 细胞通过 Ag 暴露或先前感染预先被激活的 C57BL/6 小鼠中，MAIT 细胞的积聚更为明显。胃 MAIT 细胞具有效应记忆 Tc1/Tc17 表型，并与加速性胃炎相关，其特征是中性粒细胞、巨噬细胞、树突状细胞、嗜酸性粒细胞和非 MAIT T 细胞的募集增加，以及明显的胃萎缩。用相同方法处理缺乏 MAIT 细胞的 MR1 小鼠，显示出明显较少的胃病理变化。因此，我们证明了 MAIT 细胞在与细菌相关的免疫病理学中的致病潜力，这对其他慢性细菌感染具有重要意义。
