This showed that moDCs induced greater numbers of IFN-γ selleck kinase inhibitor producing T cells and fewer IL-4-producing cells than cDCs. Co-culture of T cells with both DC subsets selectively induced greater IFN-γ responses than either component DCs subset, but this was not seen

for IL-4 (Fig. 5D). This suggests moDCs are more efficient than cDCs at driving CD4+ T cells to produce IFN-γ but can collaborate with cDCs to augment this. Lastly, in this and other studies 24, moDCs have been identified as major producers of TNF-α. To assess whether this cytokine influenced the priming of IFN-γ-producing cells, we cultured cDCs or moDCs with SM1 T cells in the presence or absence of a TNF-α-neutralizing antibody (Fig. 5E). These experiments show that neutralizing TNF-α reduces the numbers of IFN-γ-producing cells induced by moDCs but not by cDCs. Surprisingly, neutralizing TNF-α only moderated Th1 development when moDCs were cultured alone with SM1 T cells. This diminution was not seen when moDCs were co-cultured with cDCs (Fig. 5E). Therefore, moDCs can present antigen to CD4+ T cells and promote their differentiation to become IFN-γ-producing T cells. Th1 responses are characterized by the induction of IFN-γ and are essential for clearing intracellular

infections such as those caused by STm. Our studies indicate that moDCs accumulate in the T zone after STm infection, have encountered live bacteria, can present antigen to T cells and in their Wnt inhibitor absence Th1 responses are impaired. Finally, our data suggest that moDCs can act in conjunction with cDCs to perform this function. It is significant that the accumulation of moDCs is dependent upon bacterial viability rather than virulence. This offers some explanation as to why hk STm vaccines induce Th2 features but poor Th1 responses 32. The importance of viability has also been demonstrated for the recruitment of TipDCs in response to L. monocytogenes17. This suggests that inducing moDCs is likely to be a key requisite aminophylline of Th1-promoting adjuvants and that characterizing moDC induction

is likely to provide a measure of their success. Interestingly, other subunit components of the bacterium that act through TLRs, such as FliC, do not induce moDC accumulation to the same degree and this parallels the lack of Th1 response seen to flagellin in vivo 6, 33, 34. We have also observed differential Th1 or Th2 T-cell priming to OVA when presented within the bacterium or as an alum-precipitated protein respectively 35. This highlights that T-cell fate is not necessarily an intrinsic property of the T cell but dependent upon the signals received from DCs during priming. Bacterial virulence is not an important requirement for driving moDC accumulation since virulent bacteria and bacteria attenuated through two distinct mechanisms, aroA-deletion resulting in histidine auxotrophy and ssaV-deletion resulting in impaired secretion of Salmonella Pathogenicity Island II effectors, all induced moDCs to similar levels 24 h after infection.