Initial Immunopathogenesis of Multiple Sclerosis: Innate Immune Response

Figure 1

Role of innate immunity in multiple sclerosis. Glial cells, astrocytes, and microglia express a wide variety of TLRs. Stimulation with TLR ligands, dsRNA (TLR3), LPS (TLR4), peptidoglycans (PGN; TLR2 with TLR1/6), and viral CpG DNA (TLR9), promotes an array of immune functions in glial cells, including the secretion of proinflammatory cytokines, chemokines, type I interferons (IFN-α/β), and an increase in MHC classes I and II expression. TLRs activate macrophages, microglia, and dendritic cells (DCs) resulting in the production of cytokines of the innate immune system such as IL-6, IL-1β, and TNFα. These cytokines participate in blood brain barrier disruption and lymphocyte attraction to sites of inflammation, promote inflammation, and modulate adaptive immunity. For instance, IL-6 promotes Th17 and B cell differentiation. Th17 and Th1 cells and inflammation will contribute to tissue damage. Finally, MG, microglia, and DC also secrete IFNβ which, among other immunomodulatory functions, prevents leukocyte adhesion and extravasation across the blood brain barrier. Modified by Carpentier et al. [34].