M1 M2a M2b M2c Stimulation/activation IFN-γ IL4/IL13 ICs IL-10 TNF-α   LPS TGF-β LPS   TLRinteractions GCs Expression CD86 CD163 CD86 CD163 CD80 SR     IL-1R 1 CD206     TLR2 IL-1R ii     TLR4 Mouse only:     iNOS Ym1     MR Fizz1       Arg-1     Cytokines TNF-α IL-10 IL-1 IL-10 TNFSF1A TGF-β IL-10 TGF-β IL-1β IL-1ra     IL-6       IL-8       IL-12       IL-23       Chemokines when activated CCL10 CCL18     CCL9 CCL22     CCL5 CCL24     CCL4       CCL3       CCL2       CXCL 10       Enzymes Tissue degrading collagenase Tissue Remodelling and repair     Matrix Proteinases (MMP2, MMP9, Plasminogen activator) TIMP1       PDGF

Table 1: M1 and M2 subgroups. Macrophages are subdivided into the M1 classically activated and the M2 alternative activated subsets. M1 macrophages are stimulated by INF-γ, TNF-α and LPS which leads to cytokine production of TNF-α, IL-1β, IL-6, IL-8, IL-12, IL-23, CCL2, CCL3, CCL4, CCL5, CCL9 and CCL10. The M1 markers expressed include CD86, CD80, TLR2 and 4 along with iNOS and stimulate tissue degradation by secretion of enzymes such as collagenases and matrixproteinases [135]. In contrast, M2 macrophages express the scavenger receptors (SR), mannose receptor CD206 and CD163 and produce IL-10, IL1ra, CCL18, CCL22 and CCL24 and are involved in tissue remodelling and repair by secretion of TIMP1 and PDGF. The M1 subset is inhibited by IL-4 and IL-10 while the M2 subset is inhibited by IFN- γ [135].