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

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: Microglia were isolated from the brains of adult male Cx3cr1CreER/+::Csf1rFlox/Flox c57BL/6 mice fed tamoxifen chow for 12 weeks then placed back on control chow for 4 weeks. Cells were isolated by MACS using CD11b magnetic beads then FAC sorted for GFP.