Peripherally derived macrophages modulate microglial function to reduce inflammation after CNS injury

Andrew D. Greenhalgh; Juan G. Zarruk; Luke M. Healy; Sam J. Baskar Jesudasan; Priya Jhelum; Christopher K. Salmon; Albert Formanek; Matthew V. Russo; Jack P. Antel; Dorian B. Mcgavern; Barry W. Mccoll; Samuel David; Richard Daneman

doi:10.1371/journal.pbio.2005264

Peripherally derived macrophages modulate microglial function to reduce inflammation after CNS injury

Andrew D. Greenhalgh, Juan G. Zarruk, Luke M. Healy, Sam J. Baskar Jesudasan, Priya Jhelum, Christopher K. Salmon, Albert Formanek, Matthew V. Russo, Jack P. Antel, Dorian B. Mcgavern, Barry W. Mccoll, Samuel David, Richard Daneman (Editor)

Division of Neuroscience

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

Abstract

Infiltrating monocyte-derived macrophages (MDMs) and resident microglia dominate central nervous system (CNS) injury sites. Differential roles for these cell populations after injury are beginning to be uncovered. Here, we show evidence that MDMs and microglia directly communicate with one another and differentially modulate each other’s functions. Importantly, microglia-mediated phagocytosis and inflammation are suppressed by infiltrating macrophages. In the context of spinal cord injury (SCI), preventing such communication increases microglial activation and worsens functional recovery. We suggest that macrophages entering the CNS provide a regulatory mechanism that controls acute and long-term microglia-mediated inflammation, which may drive damage in a variety of CNS conditions.

Original language	English
Pages (from-to)	e2005264
Journal	PLoS Biology
Volume	16
Issue number	10
Early online date	17 Oct 2018
DOIs	https://doi.org/10.1371/journal.pbio.2005264
Publication status	E-pub ahead of print - 17 Oct 2018

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Greenhalgh, A. D., Zarruk, J. G., Healy, L. M., Baskar Jesudasan, S. J., Jhelum, P., Salmon, C. K., Formanek, A., Russo, M. V., Antel, J. P., Mcgavern, D. B., Mccoll, B. W., David, S., & Daneman, R. (Ed.) (2018). Peripherally derived macrophages modulate microglial function to reduce inflammation after CNS injury. PLoS Biology, 16(10), e2005264. Advance online publication. https://doi.org/10.1371/journal.pbio.2005264

@article{08eea954fe3f4590b4a862d328c8b59a,

title = "Peripherally derived macrophages modulate microglial function to reduce inflammation after CNS injury",

abstract = "Infiltrating monocyte-derived macrophages (MDMs) and resident microglia dominate central nervous system (CNS) injury sites. Differential roles for these cell populations after injury are beginning to be uncovered. Here, we show evidence that MDMs and microglia directly communicate with one another and differentially modulate each other{\textquoteright}s functions. Importantly, microglia-mediated phagocytosis and inflammation are suppressed by infiltrating macrophages. In the context of spinal cord injury (SCI), preventing such communication increases microglial activation and worsens functional recovery. We suggest that macrophages entering the CNS provide a regulatory mechanism that controls acute and long-term microglia-mediated inflammation, which may drive damage in a variety of CNS conditions.",

author = "Greenhalgh, {Andrew D.} and Zarruk, {Juan G.} and Healy, {Luke M.} and {Baskar Jesudasan}, {Sam J.} and Priya Jhelum and Salmon, {Christopher K.} and Albert Formanek and Russo, {Matthew V.} and Antel, {Jack P.} and Mcgavern, {Dorian B.} and Mccoll, {Barry W.} and Samuel David and Richard Daneman",

year = "2018",

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Greenhalgh, AD, Zarruk, JG, Healy, LM, Baskar Jesudasan, SJ, Jhelum, P, Salmon, CK, Formanek, A, Russo, MV, Antel, JP, Mcgavern, DB, Mccoll, BW, David, S & Daneman, R (ed.) 2018, 'Peripherally derived macrophages modulate microglial function to reduce inflammation after CNS injury', PLoS Biology, vol. 16, no. 10, pp. e2005264. https://doi.org/10.1371/journal.pbio.2005264

TY - JOUR

T1 - Peripherally derived macrophages modulate microglial function to reduce inflammation after CNS injury

AU - Greenhalgh, Andrew D.

AU - Zarruk, Juan G.

AU - Healy, Luke M.

AU - Baskar Jesudasan, Sam J.

AU - Jhelum, Priya

AU - Salmon, Christopher K.

AU - Formanek, Albert

AU - Russo, Matthew V.

AU - Antel, Jack P.

AU - Mcgavern, Dorian B.

AU - Mccoll, Barry W.

AU - David, Samuel

A2 - Daneman, Richard

PY - 2018/10/17

Y1 - 2018/10/17

N2 - Infiltrating monocyte-derived macrophages (MDMs) and resident microglia dominate central nervous system (CNS) injury sites. Differential roles for these cell populations after injury are beginning to be uncovered. Here, we show evidence that MDMs and microglia directly communicate with one another and differentially modulate each other’s functions. Importantly, microglia-mediated phagocytosis and inflammation are suppressed by infiltrating macrophages. In the context of spinal cord injury (SCI), preventing such communication increases microglial activation and worsens functional recovery. We suggest that macrophages entering the CNS provide a regulatory mechanism that controls acute and long-term microglia-mediated inflammation, which may drive damage in a variety of CNS conditions.

AB - Infiltrating monocyte-derived macrophages (MDMs) and resident microglia dominate central nervous system (CNS) injury sites. Differential roles for these cell populations after injury are beginning to be uncovered. Here, we show evidence that MDMs and microglia directly communicate with one another and differentially modulate each other’s functions. Importantly, microglia-mediated phagocytosis and inflammation are suppressed by infiltrating macrophages. In the context of spinal cord injury (SCI), preventing such communication increases microglial activation and worsens functional recovery. We suggest that macrophages entering the CNS provide a regulatory mechanism that controls acute and long-term microglia-mediated inflammation, which may drive damage in a variety of CNS conditions.

U2 - 10.1371/journal.pbio.2005264

DO - 10.1371/journal.pbio.2005264

M3 - Article

SN - 1545-7885

VL - 16

SP - e2005264

JO - PLoS Biology

JF - PLoS Biology

IS - 10

ER -

Peripherally derived macrophages modulate microglial function to reduce inflammation after CNS injury

Abstract

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