Double Roles of Macrophages in Human Neuroimmune Diseases and Their Animal Models

Table 1

Roles of macrophages in neuroimmune diseases and their animal models.

Neuroimmune diseases	Beneficial roles of macrophages	Harmful roles of macrophages	Refs
MS	Production of neurotrophic factors; Clearance of myelin debris	Secretion of inflammatory mediators; Reactivation of pathogenic T cells; Suppression of Tregs expansion	[32–34]
EAE	Eliminated debris and suppress cellular metabolism; Production of anti-inflammatory TGF-	Presenting a pathogenic role in initiating EAE; Eliminating macrophages inhibits EAE; A positive correlation between macrophage number and tissue damage in EAE	[35–37]
NMO		Participate in CDC and ADCC; Mediating proinflammatory immune mechanism through the expression of intense immunoreactivities for IFI30 and CD163	[38–40]
Rats or spinal cord cultures models for NMO		Macrophages exacerbated the severity of NMO lesions in spinal cord cultures; Depletion of macrophages reduced the severity of NMO pathology in rats; Phagocytosis; Secretion of proinflammatory cytokines	[33, 41, 42]
MG		Poliovirus-infected macrophages in thymus of several MG patients, which may be involved in the intrathymic alterations leading to MG	[43]
EAMG	Induction of apoptosis in activated T cell blasts in vitro by large suppressive macrophages which were generated from restimulating spleen cells from EAMG	Acting as APCs during the acute phase; Promoting the production of antibodies to AChR in the chronic phase	[44–46]
GBS	Secretion of anti-inflammatory cytokine IL-10	Professional antigen presentation; Secretion of cytokines and other inflammatory mediators; Phagocytosing myelin in AIDP and axons in AMAN	[47–51]
EAN	Inducing T cell apoptosis by secreting proapoptotic mediators; Secretion of IL-10 and TGF- which both can reduce the severity of EAN	Acting as APCs; Secreting proinflammatory cytokines IL-12, TNF-α, MMP-9, and iNOS that propagate inflammation and induce myelin and axonal damage; Attacking myelin or axon in a complement-dependent manner	[52–55]

AChR, acetylcholine receptor; ADCC, antibody-dependent cellular cytotoxicity; AIDP, acute inflammatory demyelinating polyneuropathy; AMAN, acute motor axonal neuropathy; APCs, antigen presenting cells; CDC, complement-dependent cytotoxicity; EAE, experimental autoimmune encephalomyelitis; EAMG, experimental autoimmune myasthenia gravis; EAN, experimental autoimmune neuritis; GBS, Guillain-Barré syndrome; IFI30, interferon gamma-inducible protein 30; IL-10, interleukin-10; IL-12, interleukin-12; iNOS, inducible nitric oxide synthase; MMP-9, matrix metalloproteinase-9; MS, multiple sclerosis; NMO, neuromyelitis optica; TGF-, transforming growth factor-; TNF-, tumor necrosis receptor-; Tregs, regulatory T cells.