Table 2. Major differences between M1 and M2 macrophages with respect to antigen presentation, activation stimuli, phenotypes expressed in various disease conditions, signaling pathway and molecules involved, biomarkers, metabolism, immune function and genes present.

Functional aspect	M1 macrophage	M2 macrophage
Antigen presentation	Yes	No
Activation stimuli	IFN-γ, TNF-α, and lipopolysaccharide (classical activation)	IL-4, IL-10, IL-13, TGF-β, glucocorticoids (alternate activation)
Metabolism	Glycolysis, HIF-1α, iNOS/NO, PKF2, mTOR, Induction of pro-inflammatory cytokines like IL-1β	OXPHOS, Arginase 1,2, AMPK, PFKFB1, Th2 type response induction, cholesterol efflux (38), efferocytosis (39)
Nature of Immune function	Pro-inflammatory killer mediated by ROS, RNS, TNFα, IL-6, IL-12, IL-23	Immunomodulation mediated by IL-10, TGFβ, PDGF, VEGF, EGF, Arginase, α-KG
Biomarkers—used in combination or isolated markers to identify macrophage subset (40)	CCL2, CCL3, CCL5; CXCL8, CXCL9, CXCL10, CXCL11, CXCL16; IL-12, TNFα, IL-6, IL-1, IL-23; CD80, CD86, NOS, ROS, MHCII, TLR2/TLR4	CCL17, CCL18, CCL22, CCL24; CXCR1, CXCR2; IL-10, IL-2RA; CD23, CD163, CD36, CD86, Mannose receptor (CD68+ MR+/CD206+MR+), scavenger receptor class A (SR-A), lectin-like oxidized LDL, Arginase, MHCII (39)
Genes/enzymes	NOS2, Ciita, IL-12 (41)	Arg1, Ym1, Fizz1, MMP12, MMP7, MERTK, Mcr1, IL-10, CD81 (41)
Signaling pathways and molecules present (41)	PI3K, p65, IRF5, STAT1, STAT2	PI3K, p50, IRF4, STAT3, STAT6
Phenotype in various disease condition	Bacterial and viral infections, auto-immune diseases (ex; Rheumatoid arthritis), obesity, diabetes, cardiovascular diseases, atherosclerosis, steatosis/fatty liver	Fibrosis, wound healing, sepsis, allergy, asthma, parasitic diseases (e.g., helminths), several tumors/cancers

α-KG, α-ketoglutarate.