The Relationship between Toll-like Receptors andHelicobacter pylori-Related Gastropathies: Still a Controversial Topic

Abstract

Innate immunity represents the first barrier against bacterial invasion. Toll-like receptors (TLRs) belong to the large family of pattern recognition receptors (PRRs), and their activation leads to the induction of inflammatory cytokines, chemokines, antigen-presenting molecules, and costimulatory molecules. Recent studies have focused on identifying the association between TLRs andHelicobacter pylori- (H. pylori-) related diseases. Therefore, this minireview focuses on assessing the role of these TLRs in the development ofH. pylori-related gastropathies. Both TLR2 and TLR were found to be involved inH. pyloriLPS recognition, with contradictory results most likely due to both the inability to obtain pure LPS in experimental studies and the heterogeneity of the bacterial LPS. In addition,TLR2was found to be the most extensively expressed gene among all the TLRs in gastric tumors. High levels of TLR4 were also associated with a higher risk of gastric cancer. TLR5 was initially associated with the recognition ofH. pyloriflagellin, but it seems that this bacterium has developed mechanisms to escape this recognition representing an important factor involved in the persistence of this infection and subsequent carcinogenesis. TLR9, the only TLR with both anti- and proinflammatory roles, was involved in the recognition ofH. pyloriDNA. The dichotomous role of TLR9, promoting or suppressing the infection, depends on the gastric environment. Recently, TLR7 and TLR8 were shown to recognize purifiedH. pyloriRNA, thereby inducing proinflammatory cytokines.TLR1andTLR10gene polymorphisms were associated with a higher risk for gastric cancer inH. pylori-infected individuals. Different gene polymorphisms of these TLRs were found to be associated with gastric cancer depending mostly on ethnicity. Further studies are required in order to develop preventive and therapeutic strategies againstH. pyloriinfections based on the functions of TLRs.