Interplay between CD8?+ dendritic cells and monocytes in response to Listeria monocytogenes infection attenuates T cell responses.

ABSTRACT: During the course of a microbial infection, different antigen presenting cells (APCs) are exposed and contribute to the ensuing immune response. CD8?(+) 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?(+) DCs are the most susceptible to infection while plasmacytoid DCs are not infected. Moreover, CD8?(+) 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 ?2 microglobulin deficient mice which lack endogenous cross-presentation. Upon infection, CD11b(+) DCs primarily secrete low levels of TNF? while CD8?(+) DCs secrete IL-12 p70. Infected monocytes secrete high levels of TNF? and IL-12p70, cytokines associated with activated inflammatory macrophages. Furthermore, co-culture of infected CD8?(+) DCs and CD11b+ DCs with monocytes enhances production of IL-12 p70 and TNF?. 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? and inducible nitric oxide synthase (iNOS). Thus these monocytes enhance IL-12 production to Lm infection, but concurrently abrogate DC-mediated T cell priming.

SUBMITTER: Kapadia D 

PROVIDER: S-EPMC3084837 | biostudies-other | 2011 Apr

REPOSITORIES: biostudies-other