It has been proposed that tRNA modification can serve as a regulatory mechanism to modulate gene expression[32]. Furthermore, it has been suggested that secreted proteins are particularly vulnerable to U34 hypomodification, and many codons in bacteria require proper U34 modification for efficient decoding [33]. Studies will need to be conducted in Salmonella to see if GidA modifies tRNA in the same fashion as in E. coli. Such studies are currently underway in this laboratory. Immunization of mice with the gidA STM mutant strain provided full protection from a lethal dose challenge of WT STM. All of the immunized mice

survived a lethal dose challenge, while all the naïve mice died within 4 days of challenge. Furthermore, none of the immunized mice displayed any visual signs of illness or septic shock associated with Salmonella Opaganib concentration infection. We chose to challenge the immunized mice with a WT STM dose of 1 x 105 CFU which is highly lethal. In our initial GidA study, this dose was approximately 1000 times higher than the LD50 of the WT STM strain [12]. We chose such a high challenge dose because we feel it is more reflective of the amount of Salmonella animals are exposed to

in the environment. Antibody CHIR-99021 supplier responses are known to contribute to Salmonella immunity [34–36]. It has been proposed that antibodies made by IgM memory B cells are Quisqualic acid the first-line defense mechanism against all infections and these antibodies are the only defense against T cell-independent antigens [37]. Studies in B cell deficient mice have shown that B cells are required for efficient protection from both primary and secondary Salmonella infection [36]. Our data indicates a strong humoral response to immunization with the gidA

mutant STM strain. The Th2 marker, IgG1, showed a marked increase in sera of mice immunized with the gidA mutant STM strain. Naïve mice receiving sera from immunized mice were more protected than naïve mice receiving a passive transfer of cells from immunized mice. Further, the level of the Th2 cytokine IL-10 showed a significant increase in induction when splenocytes from immunized mice were treated with STM cell lysate. The strong Th2 response, however, was not accompanied by an increase in IL-4 induction. IL-4, along with IL-10, induces differentiation of uncommitted T cells toward a Th2 phenotype [38, 39]. One possible explanation for this could be reasoned from the study by Okahashi et al. In their study, IL-4 knockout mice which were unable to generate classical Th2-type responses were still capable of producing significant antibody responses to inoculation with Salmonella[40]. Since Salmonella is a facultative intracellular pathogen, cellular immune responses are considered to be a crucial component of protective immunity.