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

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.