Sustained exposure to Helicobacter pylori induces immune tolerance by desensitizing TLR6

AbstractHelicobacter pylori (H. pylori, Hp) has been designated a class I carcinogen and is closely associated with severe gastric diseases. During colonization in the gastric mucosa,H. pylori develops immune escape by inducing host immune tolerance. The gastric epithelium acts as the first line of defense againstH. pylori, with Toll-like receptors (TLRs) in gastric epithelial cells being sensitive toH. pylori components and subsequently activating the innate immune system. However, the mechanism of immune tolerance induced byH. pylori through the TLR signalling pathway has not been fully elucidated. In this research, we detected the expression of TLRs and inflammatory cytokines in GES-1 cells upon sustained exposure toH. pylori orH. pylori lysate from 1 to 30 generations and in Mongolian gerbils infected withH. pylori for 5 to 90 weeks. We found that the levels of TLR6 and inflammatory cytokines first increased and then dropped during the course ofH. pylori treatment in vitro and in vivo. The restoration of TLR6 potentiated the expression of IL-1 β and IL-8 in GES-1 cells, which recruited neutrophils and reduced the colonization ofH. pylori in the gastric mucosa of gerbils. Mechanistically, we found that persistent infection withH. pylori reduces the sensitivity of TLR6 to bacterial components and regulates the expression of inflammatory cytokines in GES-1 cells through TLR6/JNK signaling. The TLR6 agonist obviously alleviated inflammation in vitro and in vivo. Promising re...
Source: Gastric Cancer - Category: Gastroenterology Source Type: research