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Isolation of Mouse Primary Microglia by Magnetic-Activated Cell Sorting in Animal Models of Demyelination
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Microglia subtypes in acute, subacute, and chronic multiple sclerosis.

John W Prineas1, Sandra Lee1

  • 1Department of Medicine, The University of Sydney, Camperdown, NSW, Australia.

Journal of Neuropathology and Experimental Neurology
|June 21, 2023
PubMed
Summary

Myelin phagocytes in multiple sclerosis (MS) originate from infiltrating monocytes, not resident microglia. Río Hortega's microglia appear to have an anti-inflammatory role in MS, contrary to current literature.

Keywords:
Microglia nodulesMonocyte encephalopathyPhagocytesRío HortegaSecondary progressive multiple sclerosisWall microglia

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Area of Science:

  • Neuroscience
  • Immunology
  • Pathology

Background:

  • Microglia are the resident immune cells of the central nervous system (CNS).
  • Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the CNS.
  • The origin of myelin phagocytes in MS lesions has been debated, with Pío del Río Hortega proposing microglia as the primary source.

Purpose of the Study:

  • To investigate microglia morphology in early and late stages of multiple sclerosis (MS).
  • To determine the origin of myelin phagocytes in MS lesions.
  • To clarify the role of microglia in the pathogenesis of MS.

Main Methods:

  • Immunohistochemical examination of archival paraffin-embedded tissue samples from 25 MS cases.
  • Analysis of microglia morphology and interaction with other immune cells.
  • Identification of specific cellular markers, including MHC class II and MRP14.

Main Results:

  • Myelin phagocytes in MS lesions were found to originate primarily from infiltrating monocytes, not resident microglia.
  • "Wall microglia" expressing MHC class II were observed at plaque margins, sometimes associated with astrocytes.
  • Microglial nodules formed by interactions between microglia and monocytes were present in chronic MS, and "activated" microglia were prominent in areas without active demyelination.

Conclusions:

  • Myelin phagocytes in MS are derived entirely from infiltrating MRP14-positive monocytes.
  • Resident microglia, as described by Río Hortega, appear to play an anti-inflammatory role in MS.
  • These findings challenge the traditional view of microglia having a destructive role in MS pathogenesis.