Peripherally derived macrophages can engraft the brain independent of irradiation and maintain an identity distinct from microglia

Peripherally derived macrophages infiltrate the brain after bone marrow transplantation and during central nervous system (CNS) inflammation. It was initially suggested that these engrafting cells were newly derived microglia and that irradiation was essential for engraftment to occur. However, it remains unclear whether brain-engrafting macrophages (beM phi s) acquire a unique phenotype in the brain, whether long-term engraftment may occur without irradiation, and whether brain function is affected by the engrafted cells. In this study, we demonstrate that chronic, partial microglia depletion is sufficient for beM phi s to populate the niche and that the presence of beM phi s does not alter behavior. Furthermore, beM phi s maintain a unique functional and transcriptional identity as compared with microglia. Overall, this study establishes beM phi s as a unique CNS cell type and demonstrates that therapeutic engraftment of beM phi s may be possible with irradiation-free conditioning regimens.