Review Article

Animal Models of MS Reveal Multiple Roles of Microglia in Disease Pathogenesis

Table 1

Functions and outcomes of microglial activation during EAE/MS.

FunctionMediatorTiming of expressionExpression levelOutcomes

Antigen PresentationActivatingMHC class I, MHC class IIAll stages (initiation, peak and recovery)Significantly increasedPresent antigen, initiate T cell activation; Induce apoptosis without co-stimulatory molecules
CD80, CD86, CD40,Depends on cell markers chosenIncreased, but lower than DCsFully activate T cell with MHC molecules
InhibitoryB1-H7Not examinedIncreasedT cell activation inhibition

Cytokine/
chemokine release
Proinflammatory (M1)IL-1β, TNF-α, IL-6, NO, IFN-γ, IL-12High at onset, sustained at all stages (initiation, peak and recovery)Dramatically increased, dominantInduce synaptic deficits; death of neurons and OLs;
Induce Th1 and Th17 differentiation;
Induce disfunction of NSCs/OPCs
Anti-inflammatory (M2)IL-4, IL-10, TGF-βLow at onset, increased at later time pointsIncreased, lower than M1Promote growth of long dendrites;
Induce Th2 and Treg differentiation;
Increase proliferation and differentiation of NSCs/OPCs
ChemokinesCCL2, CXCL3, CCL12, CCL4, CCL5VariesIncreasedRegulate migration of T cells, NSCs and OPCs

PhagocytosisActivatingCR3, SRA, FcγR, TREM2Not examinedIncreasedFacilitate recognition of myelin, remove myelin debris
InhibitorySIRPαNot examinedDecreasedDownregulate phagocytosis, induce self-tolerance