No abstract

Vesicular stomatitis virus (VSV) is a neurotropic virus that rapidly invades the central nervous system (CNS) following a single intranasal application and induces acute encephalitis essential for survival. Invasion of the CNS by inflammatory cells is thought to reflect virus-induced production of chemokines. To assess this possibility and to broadly characterize this response during the initial and acute phases of infection, brain chemokine and pro-inflammatory cytokine RNA profiles were determined in naïve and VSV-infected mice using qPCR arrays and flow cytometry. RNA transcript levels for several CC, CXC chemokines and cytokines were already elevated one day post infection with several ligand/receptor pairs co-induced which precedes peripheral leukocyte recruitment to the CNS. During acute VSV encephalitis (days 6-8), RNA levels became more robust with expression of additional chemokines and cytokines and a mixed leukocyte (previously reported). Chemokine responses associated with VSV encephalitis were blunted in mice acutely depleted of either peripheral dendritic cells or T cells. Several CC receptors for induced chemokines were highly expressed on microglia isolated from encephalitic brains. Infiltrating neutrophils and T cells failed to express these same receptors. These results suggest that different cytokines and/or chemokines may be responsible for recruitment of peripheral leukocyte subsets into the CNS, while others may drive the observed microgliosis.