Figure 1.

Microglial TREM2 in stroke pathogenesis. Ischemic stroke leads to the massive loss of neuronal tissue by triggering apoptosis and/or necrosis. In turn, the dying tissue releases damage-associated molecular pattern (DAMP) molecules including nucleotides and ECM breakdown products in addition to lipid mediators being present in myelin and neuronal debris and on the surface of apoptotic cells. These events trigger both TLR and TREM2 activation on microglia. While classically the TLR response leads to a pro-inflammatory microglial phenotype characterized by the release of pro-inflammatory cytokines, TREM2 activation appears to counteract the TLR response, leading to a decrease in the production of pro-inflammatory cytokines. Moreover, microglial TREM2 stimulates migration of microglia toward the lesion site and promotes the phagocytic clearance of apoptotic cells and debris. Finally, TREM2 was shown to be associated with a pro-regenerative microglial phenotype and the production of pro-regenerative cytokines and is suspected to play a role in microglial survival. Based on these functions of TREM2, this receptor is an attractive target for microglial modulation in the treatment of ischemic stroke. This Figure was created using Servier Medical Art licensed under a Creative Common Attribution 3.0 Generic License, available online at http://smart.servier.com/.