Regulation of the kinetics of intracerebral chemokine gene expression in murine Toxoplasma encephalitis: impact of host genetic factors.

ABSTRACT

The expression and kinetics of a panel of chemokines during Toxoplasma encephalitis (TE) were analyzed in a comparative study of genetically resistant BALB/c and susceptible C57BL/6 mice. In parallel with disease activity and the number of postinfection (p.i.) leukocytes, C57BL/6 mice induced CRG-2/IP-10, MuMIG, RANTES, MCP-1, MIP-1alpha, and MIP-1beta earlier and reached increased levels, as compared with BALB/c mice. These differences in the kinetics of intracerebral (i.c.) chemokines may serve as a compensatory mechanism to prevent death from necrotizing TE in C57BL/6 mice; in contrast, BALB/c mice downregulated i.c. chemokines with efficient parasite control in the chronic latent phase. Furthermore, this study showed that the pattern of i.c. chemokines and the cellular sources were identical in both strains of mice, with astrocytes and microglia expressing CRG-2/IP-10 and MCP-1 or RANTES and MuMIG, respectively, and leukocytes transcribing CRG-2/IP-10, MCP-1, and RANTES. Thus, the present study demonstrates that host genetic factors exert a strong impact on i.c. chemokines in experimental murine TE.