Neuronal CCL2 expression drives inflammatory monocyte infiltration into the brain during acute virus infection

Charles L Howe; Reghann G. LaFrance-Corey; Emma N Goddery; Kanish Mirchia

Our previous studies identified brain infiltration of inflammatory monocytes, a population defined as CD45 hi CD11b + Gr1 + 1A8cells, as the primary driver of hippocampal pathology during acute TMEV infection [4, 8] . We showed that animals which mount a large inflammatory monocyte response exhibit extensive loss of CA1 neurons in the dorsal hippocampus and lose the ability to learn spatial navigation and novel object recognition tasks. In contrast, mice that mount a weak inflammatory monocyte response exhibit preservation of CA1 neurons and maintain cognitive performance, despite robust virus infection [8] . In parallel, others have shown that monocyte-derived inflammatory factors such as interleukin-6 [9, 10] and tumor necrosis factor-a [11] drive ictogenesis in the TMEV model. These observations suggest that modulation of inflammatory monocyte responses during acute virus infection in the brain may confer neuroprotection. However, the specific mechanisms responsible for the recruitment of inflammatory monocytes to the brain in the TMEV model have not been previously characterized and open questions remain regarding the mechanisms of leukocyte infiltration into the brain in general.