The phenotype and corresponding function of macro-phages and microglia are shaped by a cadre of signals present in pathological tissue (Gordon and Martinez, 2010). These signals collaborate to instruct a population of cells that, at any given time, can be quite heterogeneous. To simplify this intrinsic complexity, working models of microglia and macrophage function are often used in which the cells are broadly defined using nomenclature and phenotypic signatures developed from in vitro models. For example, ‘classically’ activated M1 macrophages and ‘alternatively’ activated M2 macrophages are distinct macrophage subsets that can be generated in vitro using defined stimuli (Mosser and Edwards, 2008). Classical activation of macrophages is associated with antigen presentation and the production of inflammatory cytokines, chemokines and reactive oxygen species. Chronic persistence of M1 macrophages is thought to exacerbate disease and tissue pathology (Horn et al., 2008; Busch et al., 2009; Kigerl et al., 2009; Martinez et al., 2009; Hu et al., 2012). In contrast, M2 macrophages produce immune regulatory cytokines including TGF-β (transforming growth factor β), IL (interleukin)-10, IL-13 and IL-4 as well as wound healing molecules such as Arg1 (Arginase 1), YM1, MR (mannose receptor, CD206) and FIZZ1 (RELMα).
