Role of peripheral immune response in microglia activation and regulation of brain chemokine and proinflammatory cytokine responses induced during VSV encephalitis

•VSV encephalitis model is used to reveal brain viral clearance mechanisms.•VSV induces CCR/CXCR expression on microglia but not co-stimulatory molecules.•CNS chemokine and cytokine responses are robust, complex and biphasic.•2nd burst of VSV induced brain chemokine and cytokine production is T cell-dependent.

We report herein that neuroinvasion by vesicular stomatitis virus (VSV) activates microglia and induces a peripheral dendritic cell (DC)-dependent inflammatory response in the central nervous system (CNS). VSV neuroinvasion rapidly induces multiple brain chemokine and proinflammatory cytokine mRNAs that display bimodal kinetics. Peripheral DC ablation or T cell depletion suppresses the second wave of this response demonstrating that infiltrating T cells are primarily responsible for the bimodal characteristics of this response. The robust infiltrate associated with VSV encephalitis likely depends on sustained production of brain CCL19 and CCR7 expression on infiltrating inflammatory cells.