Helicobacter pylori promote inflammation and host defense through the cagA‐dependent activation of mTORC1

• Published in: Journal of cellular physiology Vol. 235; no. 12; pp. 10094 - 10108
• Main Authors: Feng, Guang‐Jing, Chen, Yi, Li, Ke
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.12.2020
• Subjects: Activation; Animals; Antigens, Bacterial - genetics; Antiinfectives and antibacterials; Antimicrobial peptides; Autophagy; Autophagy - genetics; Bacterial Proteins - genetics; Cell survival; Chemokines; Chemokines - genetics; Colonization; CXCL16 protein; Cytokines; Cytokines - genetics; Epithelial Cells; gastric epithelial cells; Gastric mucosa; Gastric Mucosa - microbiology; Gastric Mucosa - pathology; Gastritis; Gene Expression Regulation; Helicobacter Infections - genetics; Helicobacter Infections - microbiology; Helicobacter Infections - pathology; Helicobacter pylori; Helicobacter pylori - genetics; Helicobacter pylori - pathogenicity; Helicobacter pylori infection; Host-Parasite Interactions - genetics; Humans; Infections; Inflammation; Inflammation - genetics; Inflammation - microbiology; Inflammation - pathology; Inflammatory diseases; Interleukins; Interleukins - genetics; Intracellular Signaling Peptides and Proteins - genetics; Mechanistic Target of Rapamycin Complex 1 - genetics; Metabolism; Mice; Mice, Knockout; mTOR; mTORC1; Phagocytosis; Phosphorylation; Phosphorylation - genetics; Protein turnover; Proteins; Rapamycin; Signal Transduction - genetics; TOR protein; TOR Serine-Threonine Kinases - genetics; Transcription; mTOR; Helicobacter pylori infection; gastritis; mTORC1; gastric epithelial cells
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.29826

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. Helicobacter pylori (H. pylori) infection of gastric cells results in cagA‐dependent activation of the mechanistic target of rapamycin complex 1 (mTORC1), and mTORC1 promoted CCL7, CXCL16, and LL37 production, which might contribute to inflammation and host denfence in H. pylori infection.