Helicobacter pylori cholesteryl alpha-glucosides contribute to immune response by natural killer T cells

目前尚未确定形成胆固醇α -糖苷（aCGs）的胆固醇α -葡萄糖基转移酶（aCgT）在幽门螺杆菌感染发病机制中的作用。我们发现幽门螺杆菌临床分离株的aCgT活性与胃萎缩程度高度相关。我们研究了aCGs在免疫反应的各个方面的作用。aCGs被不变性自然杀伤T细胞（iNKT）识别，在体内和体外引发免疫应答。在iNKT细胞缺陷（Ja18 KO）或野生型小鼠中接种含有高活性aCgT的幽门螺杆菌后，与野生型小鼠相比，Ja18 KO中的细菌恢复率显著提高。此外，与野生型小鼠相比，Ja18 KO中Th1和Th2细胞的细胞因子产生特性显著降低。这些发现表明aCGs在幽门螺杆菌介导的胃炎症和癌前萎缩性胃炎中起关键作用。

It has not been determined how cholesteryl alpha-glucosyltransferase (aCgT), which forms cholesteryl alpha-glucosides (aCGs), functions in the pathogenesis of H. pylori infection. We show that the activity of aCgT from H. pylori clinical isolates is highly correlated with the degree of gastric atrophy. We investigated the role of aCGs in various aspects of the immune response. aCGs were recognized by invariant natural killer T (iNKT) cells, eliciting an immune response in vitro and in vivo. Following inoculation of H. pylori harboring highly active aCgT into iNKT cell-deficient (Ja18 KO) or wild-type mice, bacterial recovery significantly increased in Ja18 KO compared to wild-type mice. Moreover, cytokine production characteristic of Th1 and Th2 cells dramatically decreased in Ja18 KO compared to wild-type mice. These findings demonstrate that aCGs play critical roles in H. pylori-mediated gastric inflammation and precancerous atrophic gastritis.