With the development of pharmacological agents that inhibit colony-stimulating factor 1 receptor (CSF-1R) signaling and thus allow the depletion of CSF-1R-signaling-dependent cells, i.e., microglia in the CNS, several studies have proposed that microglia might be critical for host protection during viral encephalitis.32,35,48–50 These studies have examined different routes of CNS infection, such as intracranial and intranasal, from the peripheral nervous system and peripheral infection that caused encephalitis after viral entry into the CNS. This evidence concerns the gene CSF1R and viral encephalitis.