title: Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions.
abstract: 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.
authors.affiliation: Institute of Neuropathology, Georg August University, Göttingen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Mildner
authors.forename: Hauke
authors.initials: H
authors.lastname: Schmidt
authors.forename: Mirko
authors.initials: M
authors.lastname: Nitsche
authors.forename: Doron
authors.initials: D
authors.lastname: Merkler
authors.forename: Uwe-Karsten
authors.initials: UK
authors.lastname: Hanisch
authors.forename: Matthias
authors.initials: M
authors.lastname: Mack
authors.forename: Mathias
authors.initials: M
authors.lastname: Heikenwalder
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brück
authors.forename: Josef
authors.initials: J
authors.lastname: Priller
authors.forename: Marco
authors.initials: M
authors.lastname: Prinz
mesh_terms: 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
chemical_list: 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