title: The M1 and M2 paradigm of macrophage activation: time for reassessment.
abstract: Macrophages are endowed with a variety of receptors for lineage-determining growth factors, T helper (Th) cell cytokines, and B cell, host, and microbial products. In tissues, macrophages mature and are activated in a dynamic response to combinations of these stimuli to acquire specialized functional phenotypes. As for the lymphocyte system, a dichotomy has been proposed for macrophage activation: classic vs. alternative, also M1 and M2, respectively. In view of recent research about macrophage functions and the increasing number of immune-relevant ligands, a revision of the model is needed. Here, we assess how cytokines and pathogen signals influence their functional phenotypes and the evidence for M1 and M2 functions and revisit a paradigm initially based on the role of a restricted set of selected ligands in the immune response.
authors.affiliation: Botnar Research Center, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford Windmill Road, OX3 7LD, Oxford UK.
authors.forename: Fernando O
authors.initials: FO
authors.lastname: Martinez
authors.affiliation: Sir William Dunn School of Pathology, University of Oxford South Parks Road, Oxford, OX1 3RE UK.
authors.forename: Siamon
authors.initials: S
authors.lastname: Gordon