Cell-to-cell communication by microglia related extracellular vesicles

Extracellular vesicles, including exosomes and microvesicles, are small, nano-to-micrometer vesicles that are released from cells. While initially observed in immune cells and reticulocytes as vesicles meant to remove archaic proteins, now they have been observed in almost all cell types of multicellular organisms. Growing evidence indicates that extracellular vesicles, containing lipids, proteins and RNAs, represent an efficient way to transfer functional cargoes from one cell to another. In the central nervous system, the extensive cross-talk ongoing between neurons and glia, including microglia, the immune cells of the brain, takes advantage of secreted vesicles, which mediate intercellular communication over long range distance. Recent literature supports a critical role for extracellular vesicles in mediating complex and coordinated communication among neurons, astrocytes and microglia, both in the healthy and in the diseased brain. University of Zurich researchers discuss the biogenesis and function of microglia-related extracellular vesicles and focus on their putative role in Alzheimer’s disease pathology.

Cross-talk of extracellular vesicles from and to microglia

Microglia as recipient cells for EVs of different origin: 1. glioblastoma-derived EVs contain metalloproteases that modulate microglial function; 2. oligodendrocyte-derived EVs are targeted to microglia for clearance; 3. Neuron-derived EVs containing C3 can promote synaptic pruning; amyloid-beta and tau containing EVs can be taken up by microglia. 4. Circulatory EVs preferentially target microglia in the CNS. Microglia as source of EVs: ATP-dependent release of EVs, shown to contain miRNAs and cytokines, target (5.) neurons and (6.) astrocytes. A number of others stimulation agents have been described to promote EV shedding from microglia