Immune Evasion by Yersinia enterocolitica: Differential Targeting of Dendritic Cell Subpopulations In Vivo

CD4+ T cells are essential for the control of Yersinia enterocolitica (Ye) infection in mice. Ye can inhibit dendritic cell (DC) antigen uptake and degradation, maturation and subsequently T-cell activation in vitro. Here we investigated the effects of Ye infection on splenic DCs and T-cell proliferation in an experimental mouse infection model. We found that OVA-specific CD4+ T cells had a reduced potential to proliferate when stimulated with OVA after infection with Ye compared to control mice. Additionally, proliferation of OVA-specific CD4+ T cells was markedly reduced when cultured with splenic CD8a+ DCs from Ye infected mice in the presence of OVA. In contrast, T-cell proliferation was not impaired in cultures with CD4+ or CD42CD8a2 DCs isolated from Ye infected mice. However, OVA uptake and degradation as well as cytokine production were impaired in CD8a+ DCs, but not in CD4+ and CD42CD8a2 DCs after Ye infection. Pathogenicity factors (Yops) from Ye were most frequently injected into CD8a+ DCs, resulting in less MHC class II and CD86 expression than on non-injected CD8a+ DCs. Three days post infection with Ye the number of splenic CD8a+ and CD4+ DCs was reduced by 50 % and 90%, respectively. The decreased number of DC subsets, which was dependent on TLR4 and TRIF signaling, was the result of a faster proliferation and suppressed de novo DC generation. Together, we show that Ye infection negatively regulates th