CCR2 limits inflammatory functions of CD8 TRM cells that impair recognition memory during recovery from WNV encephalitis [RNA-seq]

Central nervous system (CNS) resident memory CD8 T cells (TRM) that express IFN-? have been shown to contribute to neurodegenerative processes, including synapse loss, causing memory impairment. Here, we show that CCR2 deficiency in CD8 TRM that persists within the hippocampus after recovery from CNS infection with West Nile virus (WNV) significantly contributes to poor cognitive outcomes. Using CCR2-deficient mice, we determined that CCR2 expression is not essential for CNS T cell recruitment or virologic control during acute WNV infection. However, transcriptomic analyses of forebrain CCR2+ versus CCR2- CD8 TRM during WNV recovery reveal that CCR2 expression significantly regulates hippocampal CD8 TRM phenotype and function, with increased expression of CD103, granzyme A and IFN-?. Consistent with this, WNV-recovered Cd8acreCcr2fl/fl mice exhibit decreased recognition memory. Our findings highlight CCR2's role in regulating CD8 T cell-mediated neuroinflammation and cognitive deficits, providing insights into potential therapeutic targets for CNS infections.