Microglia in Central Nervous System Inflammation and Multiple Sclerosis Pathology

• Published in: Trends in molecular medicine Vol. 25; no. 2; pp. 112 - 123
• Main Authors: Voet, Sofie, Prinz, Marco, van Loo, Geert
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2019
• Subjects: Animals; Central Nervous System - immunology; Central Nervous System - pathology; CNS; Humans; Inflammation - immunology; Inflammation - pathology; microglia; Microglia - immunology; Microglia - pathology; multiple sclerosis; Multiple Sclerosis - immunology; Multiple Sclerosis - pathology; neuroinflammation; CNS; neuroinflammation; microglia; multiple sclerosis
• ISSN: 1471-4914; 1471-499X; 1471-499X
• DOI: 10.1016/j.molmed.2018.11.005

Microglia are the resident macrophages of the central nervous system (CNS). They have important physiological functions in maintaining tissue homeostasis but also contribute to CNS pathology. Microglia respond to changes in the microenvironment, and the resulting reactive phenotype can be very diverse, with both neuroinflammatory and neuroprotective properties, illustrating the plasticity of these cells. Recent progress in understanding the autoimmune neuroinflammatory disease multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis suggests major roles for microglia in the disease, which have drastically changed our view on the function of microglia in MS. Microglia are shaped by their ontogeny and the specific CNS microenvironment, defining the functional plasticity of these cells. Microglia can respond to different types of stimuli, including exogenous infectious pathogens as well as injurious self-proteins, and initiate a neuroinflammatory response. In MS, microglia alter their transcriptional profile and become ‘disease-associated microglia’ (DAM). DAM cells in EAE display a profuse inflammatory phenotype, in contrast to other neurodegenerative diseases. In MS and EAE, microglia induce different effector functions that can be both neuroprotective and detrimental. Currently, it is believed that the initial response of microglia is beneficial, aiming to resolve the insult, but that chronic activation of microglia contributes to neurodegeneration.