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

Alexander Mildner; Hauke Schmidt; Mirko Nitsche; Doron Merkler; Uwe-Karsten Hanisch; Matthias Mack; Mathias Heikenwalder; Wolfgang Brück; Josef Priller; Marco Prinz

doi:10.1038/nn2015

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

Alexander Mildner, Hauke Schmidt, Mirko Nitsche, Doron Merkler, Uwe-Karsten Hanisch, Matthias Mack, Mathias Heikenwalder, Wolfgang Brück, Josef Priller, Marco Prinz

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	1544-53
Number of pages	10
Journal	Nature Neuroscience
Volume	10
Issue number	12
DOIs	https://doi.org/10.1038/nn2015
Publication status	Published - Dec 2007

Keywords / Materials (for Non-textual outputs)

Animals
Antigens, Ly
Axotomy
Bone Marrow Cells
Brain
Bromodeoxyuridine
Calcium-Binding Proteins
Cell Differentiation
Flow Cytometry
Gene Expression
Green Fluorescent Proteins
Lipopeptides
Lipopolysaccharides
Macrophages
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microfilament Proteins
Microglia
Monocytes
Peptides
Phosphopyruvate Hydratase
Receptors, CCR2
Stem Cell Transplantation
Journal Article
Research Support, Non-U.S. Gov't

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10.1038/nn2015

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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.",

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author = "Alexander Mildner and Hauke Schmidt and Mirko Nitsche and Doron Merkler and Uwe-Karsten Hanisch and Matthias Mack and Mathias Heikenwalder and Wolfgang Br{\"u}ck and Josef Priller and Marco Prinz",

year = "2007",

month = dec,

doi = "10.1038/nn2015",

language = "English",

volume = "10",

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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

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-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.

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-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.

KW - Animals

KW - Antigens, Ly

KW - Axotomy

KW - Bone Marrow Cells

KW - Brain

KW - Bromodeoxyuridine

KW - Calcium-Binding Proteins

KW - Cell Differentiation

KW - Flow Cytometry

KW - Gene Expression

KW - Green Fluorescent Proteins

KW - Lipopeptides

KW - Lipopolysaccharides

KW - Macrophages

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Microfilament Proteins

KW - Microglia

KW - Monocytes

KW - Peptides

KW - Phosphopyruvate Hydratase

KW - Receptors, CCR2

KW - Stem Cell Transplantation

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/nn2015

DO - 10.1038/nn2015

M3 - Article

C2 - 18026096

SN - 1097-6256

VL - 10

SP - 1544

EP - 1553

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 12

ER -

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

Abstract

Keywords / Materials (for Non-textual outputs)

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