Microglia response following acute demyelination is heterogeneous and limits infiltrating macrophage dispersion.

Autor:	Plemel JR; Hotchkiss Brain Institute and Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada.; Department of Medicine, Division of Neurology, University of Alberta, Edmonton, Alberta, Canada., Stratton JA; Hotchkiss Brain Institute and Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada., Michaels NJ; Hotchkiss Brain Institute and Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada., Rawji KS; Hotchkiss Brain Institute and Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada., Zhang E; Hotchkiss Brain Institute and Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada., Sinha S; Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada., Baaklini CS; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada.; Department of Medicine, Division of Neurology, University of Alberta, Edmonton, Alberta, Canada., Dong Y; Hotchkiss Brain Institute and Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada., Ho M; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada., Thorburn K; Department of Pharmacology, University of Alberta, Edmonton, Alberta, Canada., Friedman TN; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada., Jawad S; Hotchkiss Brain Institute and Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada., Silva C; Hotchkiss Brain Institute and Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada., Caprariello AV; Hotchkiss Brain Institute and Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada., Hoghooghi V; Hotchkiss Brain Institute and Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada., Yue J; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada., Jaffer A; Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada., Lee K; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada., Kerr BJ; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada.; Department of Anesthesiology and Pain Medicine, University of Alberta, Edmonton, Alberta, Canada., Midha R; Hotchkiss Brain Institute and Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada., Stys PK; Hotchkiss Brain Institute and Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada., Biernaskie J; Hotchkiss Brain Institute and Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.; Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada., Yong VW; Hotchkiss Brain Institute and Department of Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2020 Jan 15; Vol. 6 (3), pp. eaay6324. Date of Electronic Publication: 2020 Jan 15 (Print Publication: 2020).
DOI:	10.1126/sciadv.aay6324
Abstrakt:	Microglia and infiltrating macrophages are thought to orchestrate the central nervous system (CNS) response to injury; however, the similarities between these cells make it challenging to distinguish their relative contributions. We genetically labeled microglia and CNS-associated macrophages to distinguish them from infiltrating macrophages. Using single-cell RNA sequencing, we describe multiple microglia activation states, one of which was enriched for interferon associated signaling. Although blood-derived macrophages acutely infiltrated the demyelinated lesion, microglia progressively monopolized the lesion environment where they surrounded infiltrating macrophages. In the microglia-devoid sciatic nerve, the infiltrating macrophage response was sustained. In the CNS, the preferential proliferation of microglia and sparse microglia death contributed to microglia dominating the lesion. Microglia ablation reversed the spatial restriction of macrophages with the demyelinated spinal cord, highlighting an unrealized macrophages-microglia interaction. The restriction of peripheral inflammation by microglia may be a previously unidentified mechanism by which the CNS maintains its "immune privileged" status. (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)
Databáze:	MEDLINE
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