Alternative Activation of Macrophages: An Immunologic Functional Perspective

Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
Annual Review of Immunology (Impact Factor: 39.33). 04/2009; 27(1):451-83. DOI: 10.1146/annurev.immunol.021908.132532
Source: PubMed


Macrophages are innate immune cells with well-established roles in the primary response to pathogens, but also in tissue homeostasis, coordination of the adaptive immune response, inflammation, resolution, and repair. These cells recognize danger signals through receptors capable of inducing specialized activation programs. The classically known macrophage activation is induced by IFN-gamma, which triggers a harsh proinflammatory response that is required to kill intracellular pathogens. Macrophages also undergo alternative activation by IL-4 and IL-13, which trigger a different phenotype that is important for the immune response to parasites. Here we review the cellular sources of these cytokines, receptor signaling pathways, and induced markers and gene signatures. We draw attention to discrepancies found between mouse and human models of alternative activation. The evidence for in vivo alternative activation of macrophages is also analyzed, with nematode infection as prototypic disease. Finally, we revisit the concept of macrophage activation in the context of the immune response.

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    • "Circulating monocytes released from the bone marrow migrate to the intestine where they differentiate into resident macrophages under the influence of local cytokine milieu [24]. Recruited monocytes or resident macrophages can then be polarized to either classically activated (M1) or alternatively activated (M2) macrophages in response to LPS/IFN-c or IL-4/IL-13, respectively [28] [29] [30] [31]. M1 macrophages are characterized as inflammatory macrophages due to their high capacity in producing proinflammatory cytokines, such as TNF-a, IL-1b, IL-12, IL-23 and iNOS [29,32]. "
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    • "M2 macrophages, together with Th2 cells, remove parasites and toxins by releasing IL-4, which promotes the activation of B-cells and the production of antigen-specific antibodies [8] [33]. In addition, M2 macrophages participate in tissue repair, angiogenesis, and phagocytosis of apoptotic cells [34] [35] [36]. Thus, the reprogramming of macrophages causes changes not only in the functioning of the macrophages themselves but also in the functioning of other immune cells, thus providing the required plasticity of the immune response required for eliminating pathogenic factors. "
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    Full-text · Article · Sep 2015
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