CHEMOKINE GENE-EXPRESSION IN THE BRAINS OF MICE WITH LYMPHOCYTIC CHORIOMENINGITIS

Chemokines are pivotal in the trafficking of leukocytes. In the presen t study, we examined the expression of multiple chemokine genes during the course of lymphocytic choriomeningitis (LCM) in mice. In noninfec ted mice, no detectable chemokine gene expression was found in the bra in; however, by day 3 postinfection, the induction of a number of chem okine mRNAs was observed as follows (in order from the greatest to the least); cytokine responsive gene-2 or interferon-inducible 10-kDa pro tein (Crg-2/IP-10), RANTES, monocyte chemotactic protein-1 (MCP-1), ma crophage inflammatory protein-1 (MIP-1 beta), and MCP-3. At day 6 post infection, the expression of these chemokine mRNAs was increased, and low expression of lymphotactin, C10, MIP-2, and MIP-1 alpha mRNAs was detectable. Transcript for T-cell activation-3 was not detectable in t he brain at any time following LCM virus (LCMV) infection. With some e xceptions, a pattern of chemokine gene expression similar to that in t he brain was observed in the peripheral organs of LCMV-infected mice. Mice that lacked expression of gamma interferon developed LCM and had a qualitatively similar but quantitatively reduced cerebral chemokine gene expression profile. In contrast, little or no chemokine gene expr ession was detectable in the brains of LCMV-infected athymic mice whic h did not develop LCM. Expression of Crg-2/IP-10 RNA was localized to predominantly resident cells of the central nervous system (CNS) and o verlapped with sites of viral infection and immune cell infiltration. These findings demonstrate the expression of a number of chemokine gen es in the brains of mice infected with LCMV. The patterns of chemokine gene expression in LCM may profoundly influence the characteristic ph enotype and response of leukocytes in the brain and contribute to the immunopathogenesis of this fatal CNS infection.