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 (beMfs) 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 beMfs to populate the niche and that the presence of beMfs does not alter behavior. Furthermore, beMfs maintain a unique functional and transcriptional identity as compared with microglia. Overall, this study establishes beMfs as a unique CNS cell type and demonstrates that therapeutic engraftment of beMfs may be possible with irradiation-free conditioning regimens. Overall design: Mice were given 1000rad whole body irradiation, followed by bone marrow transplant with UBC-GFP bone marrow at 8 weeks of age. Engraftment was allowed to occur for 8 months, then engrafting macrophages and microglia were isolated from whole brains for RNA-Seq.