Characterization of differential innate and adaptive immunity against Rickettsia conorii in resistant and susceptible mice (52.14)

Abstract

Abstract Spotted fever group (SFG) rickettsiae cause severe human diseases in many endemic areas of the world. In order to identify the critical factors in determining host susceptibilities or resistance to SFG rickettsiosis, we characterized cellular immunity against R. conorii in highly susceptible C3H/HeN (C3H) mice, relatively susceptible BALB/c mice and highly resistant C57BL/6 (B6) mice. A dose of rickettsiae lethal to C3H mice is cleared by all wild type (WT) B6 and BALB/c mice in 4 days with survival. Compared to C3H mice, significantly higher expansion of natural killer (NK) cells was detected in WT B6 mice. Similar to the respective WT mice, all RAG−/− and IL-12p40−/− knockout mice on B6 background and SCID on BALB/c background survived, whereas BALB/c SCID mice with deficiency of NK cells died. These findings suggest that NK cells play a major role in the innate immunity, which is IL-12p40- independent in the resistant host. Protection against sublethal rickettsial infection in C3H mice was associated with a CD4+ Th1 cell response, the presence of greater quantities of inducible CD4+CD25+ T regulatory cells and CTL than in B6 mice. These findings suggest that a cell-mediated Th1 immune response is critical for protection against rickettsial infection in the susceptible host and T regulatory cells may contribute to the outcome of rickettsial infection, most likely through balancing T cell mediated protective immunity and immunopathology. This work was supported by a grant (AI021242) from the National Institute of Allergy and Infectious Diseases.