The role of TLRs and T cells in modulating glial activation : implications for Alzheimer's disease

Abstract

Microglia are the key immune mediators of the CNS but, while astrocytes are primarily involved in maintaining homeostasis, they also exhibit immune functions. Both microglial and astrocytic activation is associated with autoimmune and neurodegenerative diseases such as multiple sclerosis (MS), Parkinson’s disease and Alzheimer’s disease (AD). Activation by a stimulus, such as a toll like receptor (TLR) agonist, or amyloid-beta (AP) results in the rapid production and secretion of pro-inflammatory cytokines and chemokines by these cells. However, under normal conditions, microglia are maintained in a quiescent state by interaction with other cells. Specifically, activation of the microglial receptor CD200R by its ligand, which is expressed on many cells including neurons, is important in this role, and disruption of the CD200-CD200R interaction results in increased microglial activation, neuroinflammation and autoimmune inflammation.