Autophagy is a eukaryotic, nonspecific degradation mechanism and serves as part of the innate immune system of host cells. In Helicobacter pylori-infected host cells, autophagy is activated by the bacterial vacuolating cytotoxin A (VacA) via the following pathway: VacA binds to low-density lipoprotein receptor-related protein-1, induces intracellular glutathione deficiency, and enhances activation of protein kinase B (Akt), which in turn induces Mdm2-mediated p53 degradation and then activates autophagy. Translocated bacterial proteins, VacA and CagA, are degraded by autophagy. However, autophagy is not activated in the CD44v9-expressing gastric cancer stem-like cells, leading to the specific accumulation of intracellular CagA. Therefore, the presence of CD44v9-expressing cells in H. pylori-infected patients is associated with the risk of developing gastric cancer. Autophagy in the host gastric epithelial cells plays an important role in H. pylori infectious disease via degradation of VacA and CagA.
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