The Microglial membrane receptor TREM2 mediates exosome secretion to promote phagocytosis of amyloid-beta by microglia

Considerable evidence links the microglial transmembrane receptor TREM2 to the progression of Alzheimer's disease through its involvement in A beta phagocytosis by microglia. While previous studies have mainly focused on the phagocytic regulation of microglia itself, the antigen presentation of microglial exosomes in the process of immunity has been less investigated. Here, we identified TREM2 expressed on the membrane of microglial exosomes and found that it controlled exosome secretion without affecting exosome size. Microglial exosomes bind to A beta in a TREM2-dependent manner, which changes the inflammatory environment around A beta and promotes microglia to phagocytose A beta. These findings delineate a novel exosome-mediated mechanism of microglial cell-A beta crosstalk that facilitates A beta clearance under either physiological or pathological conditions in the central nervous system.

Automated summary

This study identifies TREM2 receptor expressed on the membrane of microglial exosomes and shows its involvement in controlling exosome secretion and promoting A beta clearance through microglia phagocytosis. This novel exosome-mediated mechanism provides insights into the crosstalk between microglial cells and A beta.