Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions.
Microglia are crucially important myeloid cells in the CNS and constitute the first immunological barrier against pathogens and environmental insults. The factors controlling microglia recruitment from the blood remain elusive and the direct circulating microglia precursor has not yet been identified in vivo. Using a panel of bone marrow chimeric and adoptive transfer experiments, we found that circulating Ly-6C(hi)CCR2(+) monocytes were preferentially recruited to the lesioned brain and differentiated into microglia. Notably, microglia engraftment in CNS pathologies, which are not associated with overt blood-brain barrier disruption, required previous conditioning of brain (for example, by direct tissue irradiation). Our results identify Ly-6C(hi)CCR2(+) monocytes as direct precursors of microglia in the adult brain and establish the importance of local factors in the adult CNS for microglia engraftment.
Mildner
Alexander
A
Institute of Neuropathology, Georg August University, Göttingen, Germany.
Schmidt
Hauke
H
Nitsche
Mirko
M
Merkler
Doron
D
Hanisch
Uwe-Karsten
UK
Mack
Matthias
M
Heikenwalder
Mathias
M
Brück
Wolfgang
W
Priller
Josef
J
Prinz
Marco
M
D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism*; D019771:Axotomy / Q000379:methods; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D001921:Brain / Q000166:cytology* / Q000601:surgery; D001973:Bromodeoxyuridine / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002454:Cell Differentiation; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics; D055666:Lipopeptides; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins; D017628:Microglia / Q000502:physiology*; D009000:Monocytes / Q000166:cytology* / Q000276:immunology; D010455:Peptides / Q000494:pharmacology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism*; D033581:Stem Cell Transplantation / Q000379:methods
C491049:Aif1 protein, mouse; D000950:Antigens, Ly; D002135:Calcium-Binding Proteins; C515335:Ccr2 protein, mouse; D055666:Lipopeptides; D008070:Lipopolysaccharides; D008840:Microfilament Proteins; C508075:Pam(3)CSK(4) peptide; D010455:Peptides; D054390:Receptors, CCR2; D049452:Green Fluorescent Proteins; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine