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

J Exp Med. 2018 Jun 4;215(6):1627-1647. doi: 10.1084/jem.20180247. Epub 2018 Apr 11.


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 (beMφs) 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 beMφs to populate the niche and that the presence of beMφs does not alter behavior. Furthermore, beMφs maintain a unique functional and transcriptional identity as compared with microglia. Overall, this study establishes beMφs as a unique CNS cell type and demonstrates that therapeutic engraftment of beMφs may be possible with irradiation-free conditioning regimens.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal
  • Brain / pathology*
  • Brain / radiation effects*
  • Disease Models, Animal
  • Female
  • Gamma Rays
  • Macrophages / metabolism
  • Macrophages / radiation effects*
  • Macrophages / transplantation*
  • Male
  • Mice, Inbred C57BL
  • Microglia / metabolism*
  • Microglia / radiation effects*
  • Transcription, Genetic / radiation effects