Rickettsiae-stimulated dendritic cells mediate protection against lethal rickettsial challenge in an animal model of spotted fever rickettsiosis

The role played by dendritic cells (DCs), initiators and orchestrators of the immune response, remains unclear in rickettsial infections. To investigate their importance in rickettsioses, we analyzed the responses of murine bone marrow-derived DCs (BMDCs) after rickettsial stimulation in vitro and their protective role in vivo. Rickettsia conorii stimulation of BMDCs caused significant maturation and production of proinflammatory cytokines. Transfer of rickettsiae-stimulated DCs protected mice from lethal rickettsial challenge by limiting rickettsial proliferation in vivo, whereas partial protection was observed in mice receiving lipopolysaccharide (LPS)-stimulated DCs. Immunity to R. conorii after transfer of DCs was associated with up-regulation of CD40, CD80, CD86, and major histocompatibility complex class II; with production of IL-2, IL-12, and IL-23; and with production of antigen-specific interferon-γ in T cells. Taken together, our data suggest that a vigorous proinflammatory response in DCs is associated with protective immunity to rickettsiae and that generation of antigen-specific immunity is crucial to complete protection.