The roles of macrophages and microglia in multiple sclerosis and experimental autoimmune encephalomyelitis

Multiple sclerosis (MS) is an autoimmune and neurodegenerative disorder characterized by chronic inflammation, demyelination, as well as axonal and neuronal loss in the central nervous system (CNS). Macrophages and microglia are important components of the innate immune system. They participate in the primary response to microorganisms and play a role in inflammatory responses, homeostasis, and tissue regeneration. In the initial phase of MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS, macrophages from peripheral tissues infiltrate into the CNS and, together with residential microglia, contribute to the pathogenesis of MS. In the early stages, microglia and macrophages are expressed as the M1 phenotype, which can release proinflammatory cytokines, leading to tissue damage in the CNS. However, in the later stage, the M2 phenotype, which is the phenotype that is associated with resolving inflammation and tissue repair, becomes predominant in the CNS. Therefore, it is hypothesized that the M1/M2 phenotype balance plays an important role in disease progression and that the transition from the proinflammatory M1 phenotype to the regulatory or anti-inflammatory M2 phenotype can lead to restoration of homeostasis and improved functional outcomes. This review of recent literature focuses on the discussion of the M1/M2 phenotypes of microglia and macrophages as well as their relevance in the pathophysiology and treatment of MS and EAE. Furthermore, the possibility of directing the polarization of microglia and macrophages toward the M2 phenotype as a therapeutic and preventative strategy for MS is discussed.