Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions

被引:829
作者
Mildner, Alexander
Schmidt, Hauke
Nitsche, Mirko
Merkler, Doron
Hanisch, Uwe-Karsten
Mack, Matthias
Heikenwalder, Mathias
Brueck, Wolfgang
Priller, Josef
Prinz, Marco [1 ]
机构
[1] Univ Gottingen, Inst Neuropathol, D-3400 Gottingen, Germany
[2] Univ Gottingen, Dept Radiat Oncol, D-3400 Gottingen, Germany
[3] Univ Regensburg, Dept Internal Med, D-8400 Regensburg, Germany
[4] Univ Zurich Spital, Inst Neuropathol, Zurich, Switzerland
[5] Univ Gottingen, Inst Multiple Sclerosis Res, D-3400 Gottingen, Germany
[6] Charite Univ Med Berlin, Mol Psychiat Lab, Berlin, Germany
关键词
D O I
10.1038/nn2015
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:1544 / 1553
页数:10
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