Table 1.

Differences of microglia in the M0/M1/M2 phenotype

	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 iNOS, Cox-2, IL‐1β, IL‐6, TNF‐α [35, 36]		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]	--	--	--	--
M2 (anti-inflammatory microglia) [43, 44]	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