Moreover, Harris et al. [8] reported an inverse correlation between gastric Rucaparib chemical structure Foxp3 expression and gastric pathology in H pylori�Cinfected children compared to adults. We have shown that H. pylori can induce tolerogenic programing of dendritic cells (DCs) and inhibit the host immune response [9,10] and other researchers have shown that DCs are involved in the host response to H. pylori infection [11]. Pattern recognition receptors such as the Toll-like receptors (TLRs) on antigen-presenting cells (e.g., DCs and macrophages) are important in the modulation of host immune responses. To date, 10 and 12 functional TLRs have been identified in humans and mice, respectively [12]. Each TLR recognizes distinct pathogen-associated molecular patterns (PAMPs) derived from bacteria, viruses, mycobacteria, fungi, and parasites.

TLR2, which is expressed on the surfaces of intestinal and gastric epithelial cells [13], recognizes lipopeptides from bacteria, peptidoglycans and lipoteichoic acid from gram-positive bacteria, and lipoarabinomannan from mycobacteria. Smith et al. suggested that TLR2 plays a role in the recognition of H. pylori and the subsequent induction of intracellular signaling cascades that activate inflammation [14]. In general, stimulation of the TLRs on DCs results in upregulation of costimulatory molecules, secretion of cytokines, and enhanced uptake and presentation of antigens [15]. Research indicates that TLR2 may direct tolerogenic responses. In a mouse model of Candida albicans infection, TLR2-derived signals induced immunosuppression and an increase in IL-10 production and Treg cell survival [16].

Others studies have shown that TLR2 enhances the expansion and function of CD4+CD25+ Treg cells through Foxp3 expression [17,18]. Little is known about the role of TLR2 in DC activation in response to H. pylori. In this study, we examined the role of TLRs in mediating H. pylori tolerogenic programming of DCs and their impact on anti�CH. pylori immunity. We showed in vitro that H. pylori�Cstimulated BMDCs upregulated the expression of TLR2, but not TLR4, TLR5, or TLR9. H. pylori�Cstimulated BMDCs from TLR2 knockout (TLR2KO) mice induced lower Treg and Th17 responses, but a higher IFN-�� response compared to H. pylori�Cstimulated BMDCs from wild-type (WT) mice. In vivo analyses after an H. pylori infection of 2 months duration showed lower degree of gastric H.

pylori colonization in TLR2KO mice and more severe gastritis compared to WT mice. The gastric mucosa of the infected TLR2KO mice showed lower Treg and Th17 responses, but a higher Th1 response compared Entinostat to infected WT mice. Moreover, a higher H. pylori�Cspecific Th1 response and lower Treg and Th17 responses were measured in the spleens of infected TLR2KO mice. Our data indicate TLR2 may be an important target in the modulation of the host response to H. pylori.