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

James C Cronk1,2,3,4, Anthony J Filiano1,2, Antoine Louveau1,2

  • 1Center for Brain Immunology and Glia (BIG), University of Virginia, Charlottesville, VA.

The Journal of Experimental Medicine
|April 13, 2018
PubMed

Insights

Peripherally derived macrophages can populate the brain without irradiation. These brain-engrafting macrophages (beMφs) maintain a distinct identity and do not affect brain function or behavior.

Area of Science:

  • Neuroimmunology
  • Cellular Biology
  • Neuroscience

Background:

  • Peripherally derived macrophages infiltrate the central nervous system (CNS) during inflammation and after bone marrow transplantation.
  • Previous research suggested microglia replacement by these cells and the necessity of irradiation for engraftment.

Purpose of the Study:

  • To investigate if brain-engrafting macrophages (beMφs) develop a unique phenotype in the brain.
  • To determine if long-term engraftment occurs without irradiation.
  • To assess the impact of engrafted cells on brain function.

Main Methods:

  • Chronic, partial depletion of endogenous microglia.
  • Analysis of beMφ phenotype, function, and transcriptional profile.
  • Behavioral testing in mice with engrafted beMφs.

Main Results:

  • Chronic, partial microglia depletion facilitates beMφ colonization of the brain niche.
  • Engrafted beMφs retain a unique functional and transcriptional identity distinct from microglia.
  • The presence of beMφs does not alter host behavior or brain function.

Conclusions:

  • Brain-engrafting macrophages (beMφs) represent a distinct CNS cell type.
  • Therapeutic engraftment of beMφs may be achievable using conditioning regimens that avoid irradiation.

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