Polarization of macrophages and microglia in inflammatory demyelination

Abstract

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system, and microglia and macrophages play important roles in its pathogenesis. The activation of microglia and macrophages accompanies disease development, whereas depletion of these cells significantly decreases disease severity. Microglia and macrophages usually have diverse and plastic phenotypes. Both pro-inflammatory and antiinflammatory microglia and macrophages exist in MS and its animal model, experimental autoimmune encephalomyelitis. The polarization of microglia and macrophages may underlie the differing functional properties that have been reported. in this review, we discuss the responses and polarization of microglia and macrophages in MS, and their effects on its pathogenesis and repair. Harnessing their beneficial effects by modulating their polarization states holds great promise for the treatment of inflammatory demyelinating diseases.Keywords: macrophage; microglia; polarization; demyelination; remyelination IntroductionMultiple sclerosis (MS) is a chronic autoimmune inflammatory and demyelinating disease characterized by inflammation, demyelination, axonal damage, gliosis and destruction of the blood-brain barrier [1][2][3] . Although the T-helper (Th) cells Th-1 and Th-17 were thought to be the main response effectors for autoimmune inflammation, macrophages and microglia do play an important role in the pathogenesis of MS. The pathology of newly-forming lesions in relapsingremitting MS shows only microglial activation and macrophage infiltration in demyelinating areas, with rare lymphocyte infiltration [4,5] . Moreover, macrophage depletion and microglial paralysis significantly suppress the progress of experimental autoimmune encephalomyelitis (EAE), the animal model of MS [6,7] .Macrophages and microglia play important roles in bridging the innate and adaptive immune reponses. Under normal physiological conditions, macrophages monitor the tissue environment for pathogens, maintain tissue homeostasis, phagocytose dead and dying cells, and respond rapidly to perturbations in the local environment. Microglia share many phenotypic and functional characteristics with macrophages. in the adult central nervous system (CNS), microglia are on constant surveillance for perturbations resulting from injury or disease [8] . In MS, in which pro-inflammatory, neurotoxic and myelin-attacking microglia and macrophages predominate, some microglia and macrophages with anti-inflammatory, neuroprotective and remyelinationpromoting properties are also present [9] . These conflicting lines of evidence have led to confusion and considerable debate regarding the harmful versus the beneficial roles of macrophages and microglia in MS.The polarization of macrophages and microglia may underlie their differing functional properties. Taking advantage of their beneficial effects by modulating their polarization states holds great promise for the treatment of CNS demyelinating diseases [10][11][12][13] . in this review, we discuss the ...

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