Published online May 14, 2014. doi: 10.3748/wjg.v20.i18.5244
Revised: December 13, 2013
Accepted: January 6, 2014
Published online: May 14, 2014
Helicobacter pylori (H. pylori) infects the human stomach during infancy and develops into chronic active inflammation. The majority of H. pylori tend to colonize within the mucous gel layer of the stomach. The stomach lacks its own immune function, thus innate immunity as the first line of defense is vital for specific immunity against H. pylori. We review recent discoveries in the pathophysiologic roles of toll-like receptors (TLRs), mainly TLR2 and TLR4, in H. pylori-induced inflammation. In addition, the TLR pathways activated by H. pylori-induced inflammation have been shown to be closely associated not only with gastric carcinogenesis, but also with formation of the tumor microenvironment through the production of pro-inflammatory cytokines, chemokines, and reactive oxygen species. Although the correlation between single nucleotide polymorphisms of TLRs and gastric cancer risk remains unclear, a recent study demonstrated that STAT3-driven up-regulation of TLR2 might promote gastric tumorigenesis independent of inflammation. Further research on the regulation of TLRs in H. pylori-associated gastric carcinogenesis will uncover diagnostic/predictive biomarkers and therapeutic targets for gastric cancer.
Core tip: Toll-like receptors (TLRs) play important roles not only in the first line of defense against Helicobacter pylori (H. pylori), but also in gastric carcinogenesis. TLR signaling initiated by pathogen-associated molecular patterns of H. pylori consequently works to establish antigen-specific acquired immune responses. Simultaneously, damage-associated molecular patterns produced by chronic inflammation may contribute to gastric cancer development. A better understanding of TLRs will provide new insights into new diagnostic/predictive biomarkers and therapeutic targets for H. pylori-associated gastric cancer.