Rickettsiae-Stimulated Dendritic Cells Mediate Protection against Lethal Rickettsial Challenge in an Animal Model of Spotted Fever Rickettsiosis

• Published in: The Journal of infectious diseases 2007-08, Vol.196 (4), p.629-638
• Main Authors: Jordan, Jeffrey M., Woods, Michael E., Feng, Hui-Min, Soong, Lynn, Walker, David H.
• Format: Article
• Language: English
• Subjects: Animals; Antigens; B7-1 Antigen - metabolism; B7-2 Antigen - metabolism; Bacteria; Bacterial diseases; Biological and medical sciences; Bone Marrow - immunology; Boutonneuse Fever - immunology; Boutonneuse Fever - prevention & control; CD40 Antigens - metabolism; Cells, Cultured; Coculture Techniques; Cytokines; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - transplantation; Histocompatibility Antigens Class II - metabolism; Human bacterial diseases; Immunity; Infections; Infectious diseases; Interferon-gamma - biosynthesis; Interferon-gamma - immunology; Interleukins - biosynthesis; Male; Medical sciences; Mice; Mice, Inbred C3H; Natural killer cells; Rickettsia; Rickettsia conorii; Rickettsial diseases; Species Specificity; Spleen; T lymphocytes; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Tropical bacterial diseases; Up-Regulation
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/519686

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 IL23; 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.