**, P < 0.01 for a compare with untreated

DCs. Discussion We have shown that OmpA-sal, a major virulence factor of S. enterica serovar Typhimurium, is a highly immunogenic protein that induces Th1 polarization of T cells by DC maturation. Some of the Omps from bacteria induce DC maturation and regulate Th1/Th2 immune responses [17–19]. Isibasi et al previously investigated the Omp of Salmonella as potential vaccine candidates, diagnostic antigens, and virulence factors [20]. However, the molecular mechanisms of the involvement of DCs and T cells in the immune responses still unknown. The lack of understanding of protective immunity against S. enterica serovar Typhimurium has hindered the development of an efficacious vaccine. In this study, we found that OmpA-sal PI3K inhibitor induces activation and maturation of DCs, as demonstrated by the high expression of co-stimulatory and MHC class molecules on cell surfaces and reduced endocytic activity. In addition, OmpA-sal-treated DCs induced primary T cell stimulatory activity in an allogeneic mixed lymphocyte reaction and elicited Th1 polarization through high levels of IFN-γ and low levels of IL-4. We have also shown in the current study that various concentrations of OmpA-sal induce high expression of CD80, CD86, MHC class I, and MHC class II in DCs. Moreover, OmpA-sal-treated DCs produced high levels of IL-12, but not IL-10. These data suggest

that OmpA-sal strongly induces activation and maturation of DCs, Selleck BTSA1 Protein kinase N1 and as a result DCs transmit OmpA-sal to the adaptive immune response. Successful induction of an adaptive immune response is characterized based on which antigen is presented, the dose, and the duration of presentation [21–23]. In the case of antigen recognition, an intracellular/extracelluar signaling cascade leads to activation of APCs, which in turn promotes further activation of DCs and activated T cells, and results in proliferation of T cells and their differentiation into effector T cells [5]. Accordingly, T cell proliferation in mixed lymphocyte reactions is important for efficient induction of an adaptive

immune response by interaction between DCs and T cells. In the current study, we showed that OmpA-sal remarkably stimulates T cell proliferation and IFN-γ production, which is a key cytokine of Th1 polarization through the increase in IL-12 KPT-8602 in vitro production by DCs. These findings indicate that OmpA-sal from S. enterica serovar Typhimurium can induce the Th1 immune response by DC maturation and IL-12 production. We also provide evidence that OmpA-sal activates TLR signaling pathways in DCs. The recognition of antigen by TLRs leads to activation of MAPK pathways in DCs [24]. Therefore, the activation of MAPK by OmpA-sal is a possible mechanism underlying the increased expression of IL-12 by DCs. In this study, we found that OmpA-sal binds to a TLR4 on DCs and activates MAPK signaling pathway-mediated IL-12 production.