INNATE IMMUNE CELLS ARE THE MAJOR DETERMINANTS OF HOST RESISTANCE TO MURINE SPOTTED FEVER RICKETTSIOSIS

Rong Fang¹, N. Ismail, M.D., Ph.D. ², and D. H. Walker, M.D. ¹

Departments of Pathology, UTMB

Background: Infection of C3H/HeN (C3H) mice with a lethal dose of R. conorii resulted in 100% mortality, while all C57BL/6 (B6) mice survived the same inoculum. Objective: Variations in the host innate and adaptive immune responses against infection with R. conorii in susceptible and resistant mouse strains were investigated. Methods: T cell response, expansion and function of innate immune cells and early production of chemokines and cytokines in different infected hosts were analyzed using flow cytometry, ELISA and Raybio Mouse Cytokine Antibody Array. Results: R. conorii initiated a greater cytotoxic T cell response in B6 mice compared to C3H mice and completely cleared the bacteria in four days with a vigorous innate response including greatly expanded cytotoxic NK cells, MHC-II-expressing antigen presenting cells and enhanced production of monocyte chemoattractant protein (MCP)-1, MCP-5, RANTES, and IL-12p70. NK-cell depleted SCID mice on BALB/c background succumbed to infection in 2 days while SCID BALB/c mice survived the same inoculum. Interestingly, IL-12p40-/- B6 mice showed the same resistance to infection as inbred mice, which suggested that a major difference in host resistance to R. conorii infection might be expressed at the NK cell and antigen presenting cell levels in an IL-12-independent manner. Conclusions: Our study provided useful evidence for further investigation of the mechanisms by which either R. conorii escape the immune response or host immune response controls bacterial at the early stage of infection. Supported by NIH grant AI21242.