Microglia

Abstract

As the resident macrophage (MΦ) of the brain, microglia play a crucial role in launching an appropriate immunological response to pathogens and other insults to the brain. Similar to other tissue MΦs, microglia express a large repertoire of receptors that recognise pathogen‐ and damage‐associated molecular patterns (PAMPs and DAMPs) and immunoglobulins that render them able participants in innate immunity. Consistent with this role, microglia promote adaptive immunity in the brain through antigen presentation and cytokine and chemokine production and assist in tissue repair and restoration. In addition to their immunological role, microglia participate in the development of the central nervous system (CNS) and support brain homeostasis through constant surveillance of their environment and bi‐directional communication with neurons and other glia. The significance of appropriate microglial function in CNS health is evidenced by the detrimental effect unresolved or chronic immune microglial activation has in promoting and/or advancing neuropathogenesis through microglial‐derived neurotoxic factors, as well as impaired or loss of functions that support brain homeostasis.

Key Concepts

  • Microglia are long‐lived resident macrophages within the brain parenchyma that initiate and promote immune responses in the brain to help protect it from foreign entities and/or pathological events.
  • Microglia are key players in brain development and homeostasis.
  • Bi‐directional neuron–microglia communication informs microglial activation.
  • Chronic immune activation of microglia promotes and/or contributes to the pathogenesis of many, if not all, neuropsychiatric and neurodegenerative diseases.
  • Impaired and/or loss of microglial function negatively impacts CNS homeostasis and neuronal health and function.

Keywords: microglia; macrophages; neuroinflammation; nervous system

Figure 1. ‘Resting’ microglia exhibit a highly ramified morphology. Iba‐1 immunohistochemistry of cortical grey matter from rhesus macaque without CNS disease reveals a highly ramified morphology with extensive contacts to multiple cells. 5 μm cortical grey matter at 40× magnification.
Figure 2. Microglia morphology is significantly altered in neurodegenerative disease. Iba‐1 immunohistochemistry of prefrontal cortex (Brodmann area 9) from a patient with advanced Alzheimer disease reveals significant microglial activation in white (a) and grey (b) matter. Here, microglia have retracted their processes, giving them a thickened appearance. Microglial cell bodies have also become more rounded with increased cytoplasm, as compared to ‘resting’ microglia (compare Figures and ). 5 μm prefrontal cortex at 40× magnification.
Figure 3. Microglia are intimately associated with neurons. Immunofluorescence of cortical grey matter from rhesus macaque without CNS disease. Microglia are identified by Iba‐1 positivity (red). Neurons are identified with MAP‐2 (green). Nuclei are revealed with DAPI (blue). Microglia (red, large arrow heads) are positioned in close proximity to neurons (green). Microglial processes make multiple contacts with neighboring neurons and other cells within their individual domains. Some processes appear to terminate with ‘end‐feet’ (small arrows), which increases the exposed surface area of the microglia to the cell. 5 μm cortical grey matter at 100× magnification under oil.
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Further Reading

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Fischer, Tracy(Mar 2020) Microglia. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000173.pub3]