CCR2 deficiency alters activation of microglia subsets in traumatic brain injury

In traumatic brain injury (TBI), brain resident and peripherally-derived myeloid cells are diverse in the CNS with the potential to worsen brain damage and/or to assist in healing.   We sought to better define the heterogeneity of microglia and macrophage phenotypes during TBI. We performed single-cell RNA sequencing on wildtype and Ccr2^-/-brain white cells from acute TBI and normal brain hemispheres.   Unbiased clustering uncovered 13 microglia subsets, nine monocyte/macrophage subsets, and three dendritic cell subsets.   We discovered alterations in cell numbers and transcriptional profiles of specific microglia subsets in Ccr2^-/- TBI mice compared to WT TBI mice suggesting that monocytes/macrophages influence microglia activation. Microglia phenotypes with reduced type I IFN responses accompanied neuroprotection induced by Ccr2 deficiency. Pharmacological blockade of human CCR2 after injury improved outcomes and reduced Irf7 expression.   These data expand our understanding of myeloid cell diversity, crosstalk in brain trauma, and mechanisms of neuroprotection in TBI.