Mechanistic target of rapamycin complex 1 (mTORC1) functions as regulating different cellular processes, including cell growth, proliferation, motility, survival, metabolism, autophagy, and protein transcription. Recently, it also found to be associated with many infections and inflammatory diseases, playing complex roles in pathogens growth and inflammation regulation. However, the regulation mechanism of mTORC1 in gastric epithelial cells and its role in Helicobacter pylori (H. pylori) infection and related gastritis remain unclear. Here, we identified that the phosphorylation of mechanistic target of rapamycin (mTOR) and the expression of DEP domain‐containing mTOR‐interacting protein (DEPTOR) was increased in gastric mucosa of H. pylori‐infected patients and mice, as well as in H. pylori‐infected gastric epithelial cells, which were largely depended on H. pylori cagA. The expression of DEPTOR was regulated via mTORC1, but, in turn, inhibited mTORC1. Knockdown mTOR significantly decreased expression and secretion of cytokines tumor necrosis factor‐α, interleukin‐1β, and interleukin‐6, chemokines CCL7 and CXCL16, and antimicrobial peptide LL37 in vitro, while knockdown DEPTOR had the opposite effect. Similar observations were made using mTOR knockout (KO) mice in vivo, moreover. The gastric inflammation was attenuated, while the bacterial burden was increased in mTOR KO mice during H. pylori infection. These findings supported H. pylori promote gastritis and inhibit bacterial colonization through the cagA‐dependent activation of mTORC1.

中文翻译：

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幽门螺杆菌通过依赖于cagA的mTORC1激活来促进炎症和宿主防御。

雷帕霉素复合物1（mTORC1）的机制目标是调节不同的细胞过程，包括细胞生长，增殖，运动，存活，代谢，自噬和蛋白质转录。最近，它还发现与许多感染和炎性疾病有关，在病原体生长和炎症调节中起着复杂的作用。但是，尚不清楚mTORC1在胃上皮细胞中的调控机制及其在幽门螺杆菌（H. pylori）感染和相关胃炎中的作用。在这里，我们发现，在感染了幽门螺杆菌的患者和小鼠的胃黏膜中，雷帕霉素（mTOR）的机械靶标磷酸化（mTOR）和含有DEP域的mTOR相互作用蛋白（DEPTOR）的表达均增加了。幽门螺杆菌感染的胃上皮细胞在很大程度上取决于幽门螺杆菌cagA。DEPTOR的表达是通过mTORC1调节的，但随后又抑制了mTORC1。敲除mTOR在体外显着降低了细胞因子肿瘤坏死因子α，白介素1β和白介素6，趋化因子CCL7和CXCL16以及抗菌肽LL37的表达和分泌，而敲除DEPTOR具有相反的作用。此外，在体内使用mTOR基因敲除（KO）小鼠进行了类似的观察。在幽门螺杆菌感染期间，mTOR KO小鼠的胃部炎症减轻，细菌负担增加。这些发现支持幽门螺杆菌通过cagA促进胃炎并抑制细菌定植依赖于mTORC1的激活。