Article abstract
Nature Neuroscience 10, 1544 - 1553 (2007)
Published online: 18 November 2007 | doi:10.1038/nn2015
Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions
Alexander Mildner1, Hauke Schmidt1, Mirko Nitsche2, Doron Merkler1, Uwe-Karsten Hanisch1, Matthias Mack3, Mathias Heikenwalder4, Wolfgang Brück1,5, Josef Priller6,7 & Marco Prinz1,7
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-6ChiCCR2+ 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-6ChiCCR2+ monocytes as direct precursors of microglia in the adult brain and establish the importance of local factors in the adult CNS for microglia engraftment.
- Institute of Neuropathology, Georg August University, Göttingen, Germany.
- Department of Radiation Oncology, Georg August University, Göttingen, Germany.
- Department of Internal Medicine, University of Regensburg, Regensburg, Germany.
- Institute of Neuropathology, Universitätsspital, Zurich, Switzerland.
- Institute for Multiple Sclerosis Research, Georg August University, Göttingen, Germany.
- Laboratory of Molecular Psychiatry, Charité-Universitätsmedizin Berlin, Germany.
- These authors contributed equally to this work.
Correspondence to: Marco Prinz1,7 e-mail: mprinz@med.uni-goettingen.de
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