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      Macrophage heterogeneity in tissues: phenotypic diversity and functions

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          Abstract

          During development and throughout adult life, macrophages derived from hematopoietic progenitors are seeded throughout the body, initially in the absence of inflammatory and infectious stimuli as tissue-resident cells, with enhanced recruitment, activation, and local proliferation following injury and pathologic insults. We have learned a great deal about macrophage properties ex vivo and in cell culture, but their phenotypic heterogeneity within different tissue microenvironments remains poorly characterized, although it contributes significantly to maintaining local and systemic homeostasis, pathogenesis, and possible treatment. In this review, we summarize the nature, functions, and interactions of tissue macrophage populations within their microenvironment and suggest questions for further investigation.

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          Alveolar macrophages: plasticity in a tissue-specific context.

          Tracy Hussell, Thomas Bell (2014)
          Alveolar macrophages exist in a unique microenvironment and, despite historical evidence showing that they are in close contact with the respiratory epithelium, have until recently been investigated in isolation. The microenvironment of the airway lumen has a considerable influence on many aspects of alveolar macrophage phenotype, function and turnover. As the lungs adapt to environmental challenges, so too do alveolar macrophages adapt to accommodate the ever-changing needs of the tissue. In this Review, we discuss the unique characteristics of alveolar macrophages, the mechanisms that drive their adaptation and the direct and indirect influences of epithelial cells on them. We also highlight how airway luminal macrophages function as sentinels of a healthy state and how they do not respond in a pro-inflammatory manner to antigens that do not disrupt lung structure. The unique tissue location and function of alveolar macrophages distinguish them from other macrophage populations and suggest that it is important to classify macrophages according to the site that they occupy.
          Article 0 comments Cited 539 times – based on 0 reviews     Review now
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            Immune recognition. A new receptor for beta-glucans.

            G D Brown, S. Gordon (2001)
            The carbohydrate polymers known as beta-1,3-d-glucans exert potent effects on the immune system - stimulating antitumour and antimicrobial activity, for example - by binding to receptors on macrophages and other white blood cells and activating them. Although beta-glucans are known to bind to receptors, such as complement receptor 3 (ref. 1), there is evidence that another beta-glucan receptor is present on macrophages. Here we identify this unknown receptor as dectin-1 (ref. 2), a finding that provides new insights into the innate immune recognition of beta-glucans.
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              Regulatory interactions between muscle and the immune system during muscle regeneration.

              James G. Tidball, S Villalta (2010)
              Recent discoveries reveal complex interactions between skeletal muscle and the immune system that regulate muscle regeneration. In this review, we evaluate evidence that indicates that the response of myeloid cells to muscle injury promotes muscle regeneration and growth. Acute perturbations of muscle activate a sequence of interactions between muscle and inflammatory cells. The initial inflammatory response is a characteristic Th1 inflammatory response, first dominated by neutrophils and subsequently by CD68(+) M1 macrophages. M1 macrophages can propagate the Th1 response by releasing proinflammatory cytokines and cause further tissue damage through the release of nitric oxide. Myeloid cells in the early Th1 response stimulate the proliferative phase of myogenesis through mechanisms mediated by TNF-alpha and IL-6; experimental prolongation of their presence is associated with delayed transition to the early differentiation stage of myogenesis. Subsequent invasion by CD163(+)/CD206(+) M2 macrophages attenuates M1 populations through the release of anti-inflammatory cytokines, including IL-10. M2 macrophages play a major role in promoting growth and regeneration; their absence greatly slows muscle growth following injury or modified use and inhibits muscle differentiation and regeneration. Chronic muscle injury leads to profiles of macrophage invasion and function that differ from acute injuries. For example, mdx muscular dystrophy yields invasion of muscle by M1 macrophages, but their early invasion is accompanied by a subpopulation of M2a macrophages. M2a macrophages are IL-4 receptor(+)/CD206(+) cells that reduce cytotoxicity of M1 macrophages. Subsequent invasion of dystrophic muscle by M2c macrophages is associated with progression of the regenerative phase in pathophysiology. Together, these findings show that transitions in macrophage phenotype are an essential component of muscle regeneration in vivo following acute or chronic muscle damage.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Immunol Rev
                Journal ID (iso-abbrev): Immunol. Rev
                Journal ID (publisher-id): imr
                Title: Immunological Reviews
                Publisher: John Wiley & Sons Ltd
                ISSN (Print): 0105-2896
                ISSN (Electronic): 1600-065X
                Publication date (Print): November 2014
                Publication date (Electronic): 15 October 2014
                Volume: 262
                Issue: 1
                Pages: 36-55
                Affiliations
                [1 ]Sir William Dunn School of Pathology, University of Oxford Oxford, UK
                [2 ]Nuffield Department of Primary Care Health Sciences, University of Oxford Oxford, UK
                [3 ]Botnar Research Centre, NDORMS, University of Oxford Oxford, UK
                Author notes
                Correspondence to:, Siamon Gordon, Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK, Tel.: +44 1865 275500, Fax: +44 1865 275515, e-mail: siamon.gordon@ 123456path.ox.ac.uk
                Article
                DOI: 10.1111/imr.12223
                PMC ID: 4231239
                PubMed ID: 25319326
                SO-VID: dee478d2-3da4-4f4e-bb13-2c492b69dcc6
                Copyright © © 2014 The Authors. Immunological Reviews published by John Wiley & Sons Ltd
                License:

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Subject: Invited Reviews

                Keywords: tissue macrophages,monocytes,macrophages,heterogeneity,phenotype,markers
                Data availability:
                Keywords: tissue macrophages, monocytes, macrophages, heterogeneity, phenotype, markers

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