Interplay between CD8α+ Dendritic Cells and Monocytes in Response to Listeria monocytogenes Infection Attenuates T Cell Responses

During the course of a microbial infection, different antigen presenting cells (APCs) are exposed and contribute to the ensuing immune response. CD8 alpha(+) dendritic cells (DCs) are an important coordinator of early immune responses to the intracellular bacteria Listeria monocytogenes (Lm) and are crucial for CD8(+) T cell immunity. In this study, we examine the contribution of different primary APCs to inducing immune responses against Lm. We find that CD8 alpha(+) DCs are the most susceptible to infection while plasmacytoid DCs are not infected. Moreover, CD8 alpha(+) DCs are the only DC subset capable of priming an immune response to Lm in vitro and are also the only APC studied that do so when transferred into beta 2 microglobulin deficient mice which lack endogenous cross-presentation. Upon infection, CD11b(+) DCs primarily secrete low levels of TNF alpha while CD8 alpha(+) DCs secrete IL-12 p70. Infected monocytes secrete high levels of TNFa and IL-12p70, cytokines associated with activated inflammatory macrophages. Furthermore, co-culture of infected CD8 alpha(+) DCs and CD11b(+) DCs with monocytes enhances production of IL-12 p70 and TNF alpha. However, the presence of monocytes in DC/T cell co-cultures attenuates T cell priming against Lm-derived antigens in vitro and in vivo. This suppressive activity of spleen-derived monocytes is mediated in part by both TNF alpha and inducible nitric oxide synthase (iNOS). Thus these monocytes enhance IL-12 production to Lm infection, but concurrently abrogate DC-mediated T cell priming.