Numerous gene target studies have shown the importance of CD4+ activation in resistance to Salmonella infection [41, 42]. Our data indicates a cellular immune response in mice immunized with the gidA mutant STM strain. Although the flow cytometric analysis showed no induction of memory T cells, or difference in CD8+ cells, it shows an increase in CD4+ VS-4718 population in the immunized mice at both day 7 and 42 post-immunization. It has been shown that CD4+ cells are more important than CD8+ in resistance to Salmonella infection [43,

44]. The passive transfer of cells to naïve mice from immunized mice did not confer full protection, and was not as significant as the serum passive transfer, but there was enough cell mediated immunity activated to protect a portion of the mice from a lethal dose challenge. Furthermore, RepSox nmr splenocytes from immunized mice proliferated at a much higher rate than splenocytes from control mice when treated with STM cell lysate. The IgG1 induction was significantly more prominent than the induction of IgG2a, but the level of IgG2a was still significantly higher in the immunized mice than in that of the sera of the control mice. Furthermore,

the induction of the Th1 cytokines, IL-2 and IFN-γ, shows a strong indication of cell mediated immunity induced by immunization. In particular, IFN-γ showed a marked increase in cell culture selleck supernatant when splenocytes from immunized mice were treated with STM cell lysate. The general consensus is that

the ideal Salmonella vaccine should generate both humoral and cell mediated immunity. This is due to protective immunity to Salmonella in mice being attributed to a balance between humoral and cell mediated immunity with an emphasis on development of the Th1 and Th2 subsets [45, 46]. In this study, the gidA mutant vaccine strain generated both Th1 and Th2 immunity with the Th2 immune response being the more prominent of the two. This was somewhat surprising since Salmonella is a facultative intracellular pathogen. One possible explanation for this could be found in our initial GidA study comparing the gidA mutant to the WT STM strain. The gidA mutant showed an approximate Gemcitabine in vivo 1000-fold reduction in the ability to invade T84 intestinal epithelial cells, as well as a marked reduction in ability to cause systemic infection in mice. Additionally, transcriptional and proteomic profiling identified a significant down-regulation in numerous genes and proteins responsible for invasion. Overall, the gidA mutant vaccine strain provides full protection to mice when challenged with a highly lethal dose of WT STM. The passive transfer experiments show the importance of both humoral and cell mediated immunity in this protective mechanism. This is an initial study in which a proof of principle of protective immunity has been established suggesting a gidA mutant STM strain could be a good candidate for use in a live-attenuated Salmonella vaccine.