Figure 2.

Microglial–neuronal interactions in health and disease. Healthy neurons expressing chemokine fractalkine (CX₃CL1) and CD200 membrane proteins intimately interact with their respective transmembrane protein receptors on microglia, CX₃CR1, and CD200R to sustain a down-regulated microglial phenotype. Microglial receptors have immunoreceptor tyrosine-based inhibitory motifs (ITIMs), which upon ligand–receptor activation suppresses downstream immune signaling through the recruitment of phosphatases including SHP-1. Chronic inflammation disrupts this intimate neuronal–glial interaction, thus releasing the microglial cells from a down-regulated inhibited state to an activated phenotype.