Description
Previous studies have reported that microglia depletion leads to impairment of synapse formation and these cells rapidly repopulate from CNS progenitors. However, the impact of microglia depletion and repopulation on the long-term state of the CNS environment has not been characterized. Here, we found by RNA-seq analysis that acute and synchronous microglia depletion results in a type 1-interferon inflammatory signature in degenerating somatosensory cortex in microglia-depleted mice. Transcriptomic and mass cytometry analysis of repopulated microglia demonstrates an interferon regulatory factor 7-driven activation state. Minocycline and anti-IFNAR1 antibody treatment attenuate the CNS type-1 interferon-driven inflammation and restore microglia homeostasis. Together, we found that acute microglia ablation induces a type-1 interferon activation state of grey matter microglia associated with acute neurodegeneration. Overall design: RNAseq analysis of brain cortical tissue from control and microglia-depleted mice.