Journal article
Microglia depletion exacerbates demyelination and impairs remyelination in a neurotropic coronavirus infection
Proceedings of the National Academy of Sciences - PNAS, Vol.117(39), pp.24464-24474
09/29/2020
DOI: 10.1073/pnas.2007814117
PMCID: PMC7533697
PMID: 32929007
Abstract
Microglia are considered both pathogenic and protective during recovery from demyelination, but their precise role remains ill defined. Here, using an inhibitor of colony stimulating factor 1 receptor (CSF1R), PLX5622, and mice infected with a neurotropic coronavirus (mouse hepatitis virus [MHV], strain JHMV), we show that depletion of microglia during the time of JHMV clearance resulted in impaired myelin repair and prolonged clinical disease without affecting the kinetics of virus clearance. Microglia were required only during the early stages of remyelination. Notably, large deposits of extracellular vesiculated myelin and cellular debris were detected in the spinal cords of PLX5622-treated and not control mice, which correlated with decreased numbers of oligodendrocytes in demyelinating lesions in drug-treated mice. Furthermore, gene expression analyses demonstrated differential expression of genes involved in myelin debris clearance, lipid and cholesterol recycling, and promotion of oligodendrocyte function. The results also demonstrate that microglial functions affected by depletion could not be compensated by infiltrating macrophages. Together, these results demonstrate that microglia play key roles in debris clearance and in the initiation of remyelination following infection with a neurotropic coronavirus but are not necessary during later stages of remyelination.
Details
- Title: Subtitle
- Microglia depletion exacerbates demyelination and impairs remyelination in a neurotropic coronavirus infection
- Creators
- Alan Sariol - Interdisciplinary Program in Immunology, University of Iowa, Iowa City, IA 52242Samantha Mackin - Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242Merri-Grace Allred - Interdisciplinary Program in Immunology, University of Iowa, Iowa City, IA 52242Chen Ma - School of Mathematics and Statistics, Wuhan University, 430072 Wuhan, ChinaYu Zhou - School of Mathematics and Statistics, Wuhan University, 430072 Wuhan, ChinaQinran Zhang - School of Mathematics and Statistics, Wuhan University, 430072 Wuhan, ChinaXiufen Zou - School of Mathematics and Statistics, Wuhan University, 430072 Wuhan, ChinaJuan E Abrahante - University of Minnesota Informatics Institute (UMII), Minneapolis, MN 55455David K Meyerholz - Department of Pathology, University of Iowa, Iowa City, IA 52242Stanley Perlman - Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.117(39), pp.24464-24474
- DOI
- 10.1073/pnas.2007814117
- PMID
- 32929007
- PMCID
- PMC7533697
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- National Academy of Sciences; United States
- Grant note
- T32 GM067795 / NIGMS NIH HHS R01 NS036592 / NINDS NIH HHS
- Language
- English
- Date published
- 09/29/2020
- Academic Unit
- Microbiology and Immunology; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
- Record Identifier
- 9984070668302771
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