Macrophages: a double-edged sword in experimental autoimmune encephalomyelitis

Abstract

Multiple sclerosis (MS) is a debilitating neurological disorder of the central nervous system (CNS), characterized by activation and infiltration of leukocytes and dendritic cells into the CNS. In the initial phase of MS and its animal model, experimental autoimmune encephalomyelitis (EAE), peripheral macrophages infiltrate into the CNS, where, together with residential microglia, they participate in the induction and development of disease. During the early phase, microglia/macrophages are immediately activated to become classically activated macrophages (M1 cells), release pro-inflammatory cytokines and damage CNS tissue. During the later phase, microglia/macrophages in the inflamed CNS are less activated, present as alternatively activated macrophage phenotype (M2 cells), releasing anti-inflammatory cytokines, accompanied by inflammation resolution and tissue repair. The balance between activation and polarization of M1 cells and M2 cells in the CNS is important for disease progression. Pro-inflammatory IFN-γ and IL-12 drive M1 cell polarization, while IL-4 and IL-13 drive M2 cell polarization. Given that polarized macrophages are reversible in a well-defined cytokine environment, macrophage phenotypes in the CNS can be modulated by molecular intervention. This review summarizes the detrimental and beneficial roles of microglia and macrophages in the CNS, with an emphasis on the role of M2 cells in EAE and MS patients.

Keywords: Cytokines; Experimental autoimmune encephalomyelitis; Macrophages; Multiple sclerosis.

Fig. 1.

Scheme for immune pathways leading to activation of macrophage into two subtypes. M1 cells dominantly express TNF-α, IL-1β, IL-12, NO, and induce CNS inflammation induction and tissue damage. M2 cells have specific maker CD206 (MR), dominantly express IL-4, IL-10, IL-13, TGF-β, and induce CNS inflammation resolution and tissue repair.