Gastric Mucosal Recognition ofHelicobacter pyloriIs Independent of Toll‐Like Receptor 4

Abstract

Little is known about the interactions between Helicobacter pylori, which specializes in colonizing the mucin layer that covers the gastric mucosa, and primary gastric epithelial cells. The expression pattern of Toll-like receptors (TLRs) in primary gastric epithelial cells and cell lines was compared. Primary cells did not express TLR4, whereas all cell lines expressed a nonsignaling form of TLR4. Because other cells within the mucosa expressed TLR4, it was next investigated whether H. pylori can be recognized by TLR4--they cannot. Moreover, H. pylori infection of primary cells induced a regulated production of interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha, whereas infection of cell lines only resulted in IL-8 production. The cytokine production in all cell types was strictly cag dependent. These findings indicate that, although the epithelium is important in directing the immune response against H. pylori infections, the response is independent of TLR4.

Toll-like Receptor (TLR) 2 and TLR5, but Not TLR4, Are Required for Helicobacter pylori-induced NF-κB Activation and Chemokine Expression by Epithelial Cells

“…Interestingly, Guillemin et al (34) noted that the genes whose expressions were least effected by the Cag phenotype were those involved in the immune response thus suggesting that Toll-like receptor activation may be directly responsible for the regulation of that subset. Consistent with the studies reported here, a recent report by Bä ckhed et al (15) demonstrated that regulation of gastric mucosal responses to H. pylori is TLR4-independent but cag pathogenicity island-dependent. The role of other TLRs in regulating the response to H. pylori was not addressed in those studies, however.…”

Polymorphisms in Toll-like receptor genes and risk of cancer

“…The findings by Schmausser et al (2004) contradict earlier findings by Backhed et al (2003). The latter group examined expression of TLR2, TLR4 and TLR5 in antral biopsies from 20 subjects (six infected with cagA-positive strains, nine with cagA-negative strains and five uninfected).…”

mRNA levels of TLR4 and TLR5 are independent of H pylori

“…Several studies have addressed the mRNA levels and protein expression of TLR4 and TLR5 in gastrointestinal cells or in AGS cells [6][7][8][9]13] . In this study, we examined the mRNA levels of TLR4 and TLR5 in gastric epithelial cells (biopsies and AGS cells) in order to determine if significant changes in mRNA levels could be related to the presence of H pylori or differences between the virulence of the strains.…”

“…Toll-like receptors (TLRs) are a family of mammalian homologs of the Drosophila Toll proteins and, in mammalian systems, TLR4 confers responsiveness to Gramnegative lipopolysaccharide (LPS), while TLR5 recognizes flagellin [5] . Previous studies have shown that gastric epithelia express both TLR4 and TLR5 [6][7][8][9] . Here, we studied the mRNA levels of TLR4 and TLR5 in gastric epithelial cells to determine if distinctive changes in the levels of mRNA could be affected by the presence of toxigenic and non-toxigenic (in particular vacA+ strains) H pylori strains.…”