Figure 1: Monocyte pre-programming and macrophage polarisation determine effector function of homeostatic and pathogenic tissue macrophages. Macrophage polarisation and plasticity between M2/homeostatic and M1 subsets determines effector response as antiinflammatory/ regulatory and pro-tumoral versus pro-inflammatory, immune activatory/CMI and anti-tumoral. M1-like effector functionality is indicated as an increasing scale of red colouration whereas M2-like effector functionality is indicated as an increasing scale of green colouration. M1 function is associated with iNOS/NO production, expression of pro-inflammatory cytokines (TNFα, IL-12 and IL-23), hence Th1 and Th17-mediated CMI. Pathogenic association of M1 function is linked with inflammatory diseases such as CD and CP. M2 function is associated with Arg-1 activity, expression of suppressive cytokines, hence Th2 and Treg-mediated responses. Pathogenic association of M2 function is linked with immunosuppressive diseases such as OSCC and localised pro-tumoral environments of solid tumours. Just how preprogrammed monocyte subsets link in to the development of M1- or M2-like Mφ responses is not fully defined and is subject to speculation (hence ????? indicated). Classical CD16-negative monocytes are depicted in green and non-classical CD16-positive monocytes in red. These monocyte subsets correspond to the M1 and M2 subsets with respect to pro-inflammatory and anti-inflammatory/regulatory cytokine production whereas both subsets express iNOS. In contrast, the intermediate monocyte subset expresses Arg-1, normally associated with regulatory, M2-like function. Thus, monocyte subsets do not exactly align with Mφ subsets, but may be representative of a sliding scale of effector functionality determined by a combination of pre-programming, differentiation and activation signals representative of the localised tissue environment in homeostatic, pathogenic challenge or disease status.