From: Different phenotypes of microglia in animal models of Alzheimer disease
Possible markers | Morphological appearance | Activation pathway | Function | Secreted factors | Effect of fatty acids on microglia | Chemokines | Main energy source | ||
---|---|---|---|---|---|---|---|---|---|
M0 (Homeostatic microglia) | CD11b, P2ry12, Cx3cr1, Tmem119, Sall1, Tgfbr1, Fcrls, Hexb, Mertk, Gpr34, Olfml3, Siglech [32] | Branched, have small somata and multiple fine processes [33]) | – | Have housekeeping functions and typically express genes involved in synaptic pruning, remodeling, and phagocytosis [34] | Soluble factors, including TNF-α and BDNF | – | CCL2 | – | |
M1 (pro-inflammatory microglia) | CD86, CD16/32, MHC-11, CD40, IFN-γ CD11b, CCL2 | Larger somata and still branched compared with M0 | LPS and IFN-γ [37] | Pro-inflammatory and pro-killing functions | TNF-α, IL-6, IL-12, IL-1β, IL-18, CXCL10, NO, ROS, iNOS, and proteolytic enzymes (MMP9, MMP3) [38] | saturated fatty acids increase the pro-inflammatory microglial phenotype | CCL2、CCL3、CCL4、CCL5、CXCL1、CXCL8、CXCL9、CXCL10 | Preferentially use glycolysis [39] | |
M1½ | co-expressing M1 makers and M2 markers [40] | Bipolar-shaped microglia [41] | -- | improve cognition [42] | -- | -- | -- | -- | |
M2a | CD206, SRs Arg1, Fizz-1 , YM1, CCL22 | Amoeboid morphology [45] | IL-4 or IL-13 [46] | Involved in phagocytosis, tissue restoration, and tissue regeneration | IL-10, IGF-1, and trophic polyamines | Unsaturated fatty acids influence the anti-inflammatory microglial phenotype [46] | CCL22、CXCL8、CXCL12、CX3CL1 | Oxidative phosphorylation and fatty acid oxidation [39] | |
M2b | CD86, MHC II TNF-α, IL-6, IL-10, COX2 | TLRs, FCγ and IL-1 receptors [47] | Involved in the recruitment of regulatory T cells | TNF-α, IL-1β, IL-10, and IL-6 | |||||
M2c | SLAM, CD206 TGFβ, IL-10, CD163 [48] | IL-10, TGF-β, and glucocorticoid hormones, sphingosine kinase, and CD163. A membrane-bound receptor for haptoglobin/hemoglobin complexes [49] | Involved in anti-inflammatory and therapeutic functions | TGF-β, IL-10, sphingosine lipid kinase |