Differential requirement of CD8α+/CD103+ dendritic cells for bacterial dissemination versus T cell priming following mucosal infection with Listeria monocytogenes (P3060)

Abstract

Abstract Dendritic cells (DCs) are essential in priming CD8+ T cells to bacterial pathogens, such as Listeria monocytogenes (Lm). Interestingly, recent studies suggest that DCs also function in systemic dissemination of Lm, following an i.v. route of infection, as evidenced by the 2 log lower bacterial burden in BatF3-/- mice, which lack both CD8α+ and CD103+ DCs, than in wild-type (WT) mice. Lm infection, however, typically occurs via the mucosal route in humans through the binding of Lm internalin A (InlA) to E-cadherin on the surface of epithelial cells. Since murine E-cadherin does not bind InlA, we generated a “murinized” Lm strain that expresses a modified form of InlA that binds murine E-cadherin in order to test whether DCs are required for bacterial dissemination following a mucosal route of infection. In agreement with the previous study, we found that the bacterial burden was significantly reduced in BatF3-/- mice relative to WT mice, when infected i.v. with murinized Lm. By contrast, there were no significant differences in bacterial burden in BatF3-/- and WT mice following mucosal infection (intragastric and intranasal) with murinized Lm. Surprisingly, despite similar bacterial burden, BatF3-/- mice were unable to prime an Lm-specific CD8+ T cell response. Together, these data demonstrate that, following mucosal Lm infection, CD8α+ and CD103+ DCs are dispensable for systemic dissemination, but are indispensable for priming a CD8+ T cell response.