Association of TLR4 and Treg in Helicobacter pylori Colonization and Inflammation in Mice

The host immune response plays an important role in the pathogenesis of Helicobacter pylori infection. The aim of this study was to clarify the immune pathogenic mechanism of Helicobacter pylori infection via TLR signaling and gastric mucosal Treg cells in mice. To discover the underlying mechanism, we selectively blocked the TLR signaling pathway and subpopulations of regulatory T cells in the gastric mucosa of mice, and examined the consequences on H. pylori infection and inflammatory response as measured by MyD88, NF-kappa B p65, and Foxp3 protein expression levels and the levels of Th1, Th17 and Th2 cytokines in the gastric mucosa. We determined that blocking TLR4 signaling in H. pylori infected mice decreased the numbers of Th1 and Th17 Treg cells compared to controls (P < 0.001-0.05), depressed the immune response as measured by inflammatory grade (P < 0.05), and enhanced H. pylori colonization (P < 0.05). In contrast, blocking CD25 had the opposite effects, wherein the Th1 and Th17 cell numbers were increased (P < 0.001-0.05), immune response was enhanced (P < 0.05), and H. pylori colonization was inhibited (P < 0.05) compared to the non-blocked group. In both blocked groups, the Th2 cytokine IL-4 remained unchanged, although IL-10 in the CD25 blocked group was significantly decreased (P < 0.05). Furthermore, MyD88, NF-kappa B p65, and Foxp3 in the non-blocked group were significantly lower than those in the TLR4 blocked group (P < 0.05), but significantly higher than those of the CD25 blocked group (P < 0.05). Together, these results suggest that there might be an interaction between TLR signaling and Treg cells that is important for limiting H. pylori colonization and suppressing the inflammatory response of infected mice.