Distinct in vivo dendritic cell activation by live versus killed Listeria monocytogenes

Abstract

Immunization of mice with live or heat-killed Listeria monocytogenes (HKLM) efficiently primes pathogen-specific CD8 + T cells. T lymphocytes primed by HKLM, however, undergo attenuated proliferation and do not fully differentiate. Thus, only infection with live bacteria induces long-term, CD8 + T cell-mediated protective immunity. In this study we demonstrate that live and heat-killed bacteria, while both associating with Mac-3 + CD11b hi cells, localize to distinct splenic areas following intravenous inoculation. While HKLM localize to the marginal zone and the splenic red pulp, live L. monocytogenes are carried to the T cell zone of splenic white pulp. Despite these differences, in vivo depletion of CD11c-expressing cells prevents priming of naive T cells by either HKLM or live L. monocytogenes. Analysis of CD11c hi dendritic cells (DC) reveals that infection with live L. monocytogenes induces higher levels of CD40, CD80 and CD86 expression than immunization with HKLM. Our results suggest that CD8 + T cell priming following HKLM immunization or live infection is mediated by DC and that the disparate outcomes of priming can be attributed to suboptimal conditioning of DC in the absence of live, cytosol-invasive bacteria.

Suppression of the Bacterial Antigen‐Specific T Cell Response and the Dendritic Cell Migration to the Lymph Nodes by Osteopontin

“…In addition, the essential role of DC to elicit T cell immune response in listerial infection has been reported (10,25). Therefore, we next examined the influence of OPN on DC.…”

CD8 T Cell Recall Responses Are Regulated by the Tissue Tropism of the Memory Cell and Pathogen

“…The reasons that VSV and LM infections induce memory CD8 T cell reactivation at distinct locations are not entirely clear. Both infectious agents have been shown to infect cell types in the spleen, particularly macrophages (54,55). Thus, why VSV specific CD8 T cells appear to be preferentially activated in the LN is not obvious but activation of LM-specific CD8 T cells in the spleen is perhaps not surprising given the predilection for LM to replicate in this tissue.…”

Innate and adaptive immune responses to Listeria monocytogenes: a short overview

“…In vivo experiments have complemented in vitro findings. Splenic DCs from mice infected with live L. monocytogenes express higher surface levels of the co-stimulatory molecules CD40, CD80, and CD86 than mice immunized with heat-killed bacteria [44].…”