TY - JOUR
T1 - Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions
AU - Mildner, Alexander
AU - Schmidt, Hauke
AU - Nitsche, Mirko
AU - Merkler, Doron
AU - Hanisch, Uwe Karsten
AU - Mack, Matthias
AU - Heikenwalder, Mathias
AU - Brück, Wolfgang
AU - Priller, Josef
AU - Prinz, Marco
N1 - Funding Information:
We thank O. Kowatsch, M. Schedensack, E. Pralle, P. Grämmel and S. Blumenau for excellent technical assistance. We thank S. Jung (Rehovot, Israel) for scientific input. This work was supported by grants from Gemeinnützige Hertie-Stiftung to M.P. and D.M., Deutsche Forschungsgemeinschaft (SFB 507 A5 and PR 577) to J.P. and M.P. This project was supported by the DFG research Center for Molecular Physiology of the Brain Göttingen, but support was unfortunately discontinued. M.H. is supported by the Swiss MS Society and the Prof. Dr. Max-Cloëtta Foundation. A.M. and H.S. are fellows of the Gertrud Reemtsma Foundation.
PY - 2007/12
Y1 - 2007/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=36448955070&partnerID=8YFLogxK
U2 - 10.1038/nn2015
DO - 10.1038/nn2015
M3 - Article
C2 - 18026096
AN - SCOPUS:36448955070
SN - 1097-6256
VL - 10
SP - 1544
EP - 1553
JO - Nature Neuroscience
JF - Nature Neuroscience
IS - 12
ER -