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Annual Review of Pathology Jan 2020Macrophages are a diverse set of cells present in all body compartments. This diversity is imprinted by their ontogenetic origin (embryonal versus adult bone... (Review)
Review
Macrophages are a diverse set of cells present in all body compartments. This diversity is imprinted by their ontogenetic origin (embryonal versus adult bone marrow-derived cells); the organ context; by their activation or deactivation by various signals in the contexts of microbial invasion, tissue damage, and metabolic derangement; and by polarization of adaptive T cell responses. Classic adaptive responses of macrophages include tolerance, priming, and a wide spectrum of activation states, including M1, M2, or M2-like. Moreover, macrophages can retain long-term imprinting of microbial encounters (trained innate immunity). Single-cell analysis of mononuclear phagocytes in health and disease has added a new dimension to our understanding of the diversity of macrophage differentiation and activation. Epigenetic landscapes, transcription factors, and microRNA networks underlie the adaptability of macrophages to different environmental cues. Macrophage plasticity, an essential component of chronic inflammation, and its involvement in diverse human diseases, most notably cancer, is discussed here as a paradigm.
Topics: Animals; Cell Plasticity; Humans; Immunity, Innate; Inflammation; Macrophage Activation; Macrophages; Neoplasms; Signal Transduction; Transcription Factors
PubMed: 31530089
DOI: 10.1146/annurev-pathmechdis-012418-012718 -
Nature Reviews. Immunology Dec 2008Macrophages display remarkable plasticity and can change their physiology in response to environmental cues. These changes can give rise to different populations of... (Review)
Review
Macrophages display remarkable plasticity and can change their physiology in response to environmental cues. These changes can give rise to different populations of cells with distinct functions. In this Review we suggest a new grouping of macrophage populations based on three different homeostatic activities - host defence, wound healing and immune regulation. We propose that similarly to primary colours, these three basic macrophage populations can blend into various other 'shades' of activation. We characterize each population and provide examples of macrophages from specific disease states that have the characteristics of one or more of these populations.
Topics: Animals; Cytokines; Humans; Immunity, Innate; Inflammation; Macrophage Activation; Macrophages; Wound Healing
PubMed: 19029990
DOI: 10.1038/nri2448 -
Frontiers in Immunology 2021Macrophages are important immune cells in innate immunity, and have remarkable heterogeneity and polarization. Under pathological conditions, in addition to the resident... (Review)
Review
Macrophages are important immune cells in innate immunity, and have remarkable heterogeneity and polarization. Under pathological conditions, in addition to the resident macrophages, other macrophages are also recruited to the diseased tissues, and polarize to various phenotypes (mainly M1 and M2) under the stimulation of various factors in the microenvironment, thus playing different roles and functions. Liver diseases are hepatic pathological changes caused by a variety of pathogenic factors (viruses, alcohol, drugs, etc.), including acute liver injury, viral hepatitis, alcoholic liver disease, metabolic-associated fatty liver disease, liver fibrosis, and hepatocellular carcinoma. Recent studies have shown that macrophage polarization plays an important role in the initiation and development of liver diseases. However, because both macrophage polarization and the pathogenesis of liver diseases are complex, the role and mechanism of macrophage polarization in liver diseases need to be further clarified. Therefore, the origin of hepatic macrophages, and the phenotypes and mechanisms of macrophage polarization are reviewed first in this paper. It is found that macrophage polarization involves several molecular mechanisms, mainly including TLR4/NF-κB, JAK/STATs, TGF-β/Smads, PPARγ, Notch, and miRNA signaling pathways. In addition, this paper also expounds the role and mechanism of macrophage polarization in various liver diseases, which aims to provide references for further research of macrophage polarization in liver diseases, contributing to the therapeutic strategy of ameliorating liver diseases by modulating macrophage polarization.
Topics: Animals; Biomarkers; Cell Differentiation; Cell Plasticity; Diagnosis, Differential; Disease Susceptibility; Energy Metabolism; Gene Expression Regulation; Humans; Liver Diseases; Macrophage Activation; Macrophages; Organ Specificity; Phenotype; Signal Transduction
PubMed: 34970275
DOI: 10.3389/fimmu.2021.803037 -
International Journal of Molecular... Jun 2021The M1/M2 macrophage paradigm plays a key role in tumor progression. M1 macrophages are historically regarded as anti-tumor, while M2-polarized macrophages, commonly... (Review)
Review
The M1/M2 macrophage paradigm plays a key role in tumor progression. M1 macrophages are historically regarded as anti-tumor, while M2-polarized macrophages, commonly deemed tumor-associated macrophages (TAMs), are contributors to many pro-tumorigenic outcomes in cancer through angiogenic and lymphangiogenic regulation, immune suppression, hypoxia induction, tumor cell proliferation, and metastasis. The tumor microenvironment (TME) can influence macrophage recruitment and polarization, giving way to these pro-tumorigenic outcomes. Investigating TME-induced macrophage polarization is critical for further understanding of TAM-related pro-tumor outcomes and potential development of new therapeutic approaches. This review explores the current understanding of TME-induced macrophage polarization and the role of M2-polarized macrophages in promoting tumor progression.
Topics: Animals; Biomarkers; Cell Transformation, Neoplastic; Cytokines; Humans; Hypoxia; Immunophenotyping; Inflammation; Macrophage Activation; Neoplasm Metastasis; Neoplasm Staging; Signal Transduction; Tumor Microenvironment; Tumor-Associated Macrophages
PubMed: 34209703
DOI: 10.3390/ijms22136995 -
Frontiers in Immunology 2019Macrophages are found in tissues, body cavities, and mucosal surfaces. Most tissue macrophages are seeded in the early embryo before definitive hematopoiesis is... (Comparative Study)
Comparative Study Review
Macrophages are found in tissues, body cavities, and mucosal surfaces. Most tissue macrophages are seeded in the early embryo before definitive hematopoiesis is established. Others are derived from blood monocytes. The macrophage lineage diversification and plasticity are key aspects of their functionality. Macrophages can also be generated from monocytes and undergo classical (LPS+IFN-γ) or alternative (IL-4) activation. , macrophages with different polarization and different activation markers coexist in tissues. Certain mouse strains preferentially promote T-helper-1 (Th1) responses and others Th2 responses. Their macrophages preferentially induce iNOS or arginase and have been called M1 and M2, respectively. In many publications, M1 and classically activated and M2 and alternatively activated are used interchangeably. We tested whether this is justified by comparing the gene lists positively [M1(=LPS+)] or negatively [M2(=LPS-)] correlated with the ratio of and in transcriptomes of LPS-treated peritoneal macrophages with classically (LPS, IFN-γ) vs. alternatively activated (IL-4) bone marrow derived macrophages, both from published datasets. Although there is some overlap between M1(=LPS+) and classically activated (LPS+IFN-γ) and M2(=LPS-) and alternatively activated macrophages, many more genes are regulated in opposite or unrelated ways. Thus, M1(=LPS+) macrophages are not equivalent to classically activated, and M2(=LPS-) macrophages are not equivalent to alternatively activated macrophages. This fundamental discrepancy explains why most surface markers identified on generated macrophages do not translate to the situation. Valid M1/M2 surface markers remain to be discovered.
Topics: Animals; Arginine; Cell Movement; Cell Polarity; Chemotaxis; Humans; Lipid Metabolism; Lipopolysaccharides; Macrophage Activation; Macrophages; Mice; Protein Processing, Post-Translational; Signal Transduction
PubMed: 31178859
DOI: 10.3389/fimmu.2019.01084 -
Frontiers in Immunology 2019The immunology of pregnancy is complex and poorly defined. During the complex process of pregnancy, macrophages secrete many cytokines/chemokines and play pivotal roles... (Review)
Review
The immunology of pregnancy is complex and poorly defined. During the complex process of pregnancy, macrophages secrete many cytokines/chemokines and play pivotal roles in the maintenance of maternal-fetal tolerance. Here, we summarized the current knowledge of macrophage polarization and the mechanisms involved in physiological or pathological pregnancy processes, including miscarriage, preeclampsia, and preterm birth. Although current evidence provides a compelling argument that macrophages are important in pregnancy, our understanding of the roles and mechanisms of macrophages in pregnancy is still rudimentary. Since macrophages exhibit functional plasticity, they may be ideal targets for therapeutic manipulation during pathological pregnancy. Additional studies are needed to better define the functions and mechanisms of various macrophage subsets in both normal and pathological pregnancy.
Topics: Female; Humans; Macrophage Activation; Macrophages; Pregnancy; Pregnancy Complications
PubMed: 31037072
DOI: 10.3389/fimmu.2019.00792 -
Journal of Leukocyte Biology Aug 2019Macrophages play an important role in a wide variety of physiologic and pathologic processes. Plasticity and functional polarization are hallmarks of macrophages.... (Review)
Review
Macrophages play an important role in a wide variety of physiologic and pathologic processes. Plasticity and functional polarization are hallmarks of macrophages. Macrophages commonly exist in two distinct subsets: classically activated macrophages (M1) and alternatively activated macrophages (M2). M2b, a subtype of M2 macrophages, has attracted increasing attention over the past decade due to its strong immune-regulated and anti-inflammatory effects. A wide variety of stimuli and multiple factors modulate M2b macrophage polarization in vitro and in vivo. M2b macrophages possess both protective and pathogenic roles in various diseases. Understanding the mechanisms of M2b macrophage activation and the modulation of their polarization might provide a great perspective for the design of novel therapeutic strategies. The purpose of this review is to discuss current knowledge of M2b macrophage polarization, the roles of M2b macrophages in a variety of diseases and the stimuli to modulate M2b macrophage polarization.
Topics: Animals; Biomarkers; Disease Susceptibility; Gene Expression Regulation; Humans; Immunomodulation; Immunophenotyping; Macrophage Activation; Macrophages; Phenotype; Signal Transduction
PubMed: 30576000
DOI: 10.1002/JLB.3RU1018-378RR -
Nature Reviews. Clinical Oncology Jul 2017Macrophages are crucial drivers of tumour-promoting inflammation. Tumour-associated macrophages (TAMs) contribute to tumour progression at different levels: by promoting... (Review)
Review
Macrophages are crucial drivers of tumour-promoting inflammation. Tumour-associated macrophages (TAMs) contribute to tumour progression at different levels: by promoting genetic instability, nurturing cancer stem cells, supporting metastasis, and taming protective adaptive immunity. TAMs can exert a dual, yin-yang influence on the effectiveness of cytoreductive therapies (chemotherapy and radiotherapy), either antagonizing the antitumour activity of these treatments by orchestrating a tumour-promoting, tissue-repair response or, instead, enhancing the overall antineoplastic effect. TAMs express molecular triggers of checkpoint proteins that regulate T-cell activation, and are targets of certain checkpoint-blockade immunotherapies. Other macrophage-centred approaches to anticancer therapy are under investigation, and include: inhibition of macrophage recruitment to, and/or survival in, tumours; functional re-education of TAMs to an antitumour, 'M1-like' mode; and tumour-targeting monoclonal antibodies that elicit macrophage-mediated extracellular killing, or phagocytosis and intracellular destruction of cancer cells. The evidence supporting these strategies is reviewed herein. We surmise that TAMs can provide tools to tailor the use of cytoreductive therapies and immunotherapy in a personalized medicine approach, and that TAM-focused therapeutic strategies have the potential to complement and synergize with both chemotherapy and immunotherapy.
Topics: Antineoplastic Agents; Humans; Macrophage Activation; Macrophages; Molecular Targeted Therapy; Neoplasms
PubMed: 28117416
DOI: 10.1038/nrclinonc.2016.217 -
Frontiers in Immunology 2021This mini-review summarizes the current evidence for the role of macrophage activation and polarization in inflammation and immune response pertinent to interstitial... (Review)
Review
This mini-review summarizes the current evidence for the role of macrophage activation and polarization in inflammation and immune response pertinent to interstitial lung disease, specifically pulmonary fibrosis. In the fibrosing lung, the production and function of inflammatory and fibrogenic mediators involved in the disease development have been reported to be regulated by the effects of polarized M1/M2 macrophage populations. The M1 and M2 macrophage phenotypes were suggested to correspond with the pro-inflammatory and pro-fibrogenic signatures, respectively. These responses towards tissue injury followed by the development and progression of lung fibrosis are further regulated by macrophage-derived microRNAs (miRNAs). Besides cellular miRNAs, extracellular exosomal-miRNAs derived from M2 macrophages have also been proposed to promote the progression of pulmonary fibrosis. In a future perspective, harnessing the noncoding miRNAs with a key role in the macrophage polarization is, therefore, suggested as a promising therapeutic strategy for this debilitating disease.
Topics: Animals; Biomarkers; Cell Plasticity; Cytokines; Disease Susceptibility; Exosomes; Gene Expression Regulation; Humans; Inflammation Mediators; Macrophage Activation; Macrophages; MicroRNAs; Models, Biological; Pulmonary Fibrosis
PubMed: 34489932
DOI: 10.3389/fimmu.2021.678457 -
Immunology Jun 2018Macrophages are extremely heterogeneous and plastic cells with an important role not only in physiological conditions, but also during inflammation (both for initiation... (Review)
Review
Macrophages are extremely heterogeneous and plastic cells with an important role not only in physiological conditions, but also during inflammation (both for initiation and resolution). In the early 1990s, two different phenotypes of macrophages were described: one of them called classically activated (or inflammatory) macrophages (M1) and the other alternatively activated (or wound-healing) macrophages (M2). Currently, it is known that functional polarization of macrophages into only two groups is an over-simplified description of macrophage heterogeneity and plasticity; indeed, it is necessary to consider a continuum of functional states. Overall, the current available data indicate that macrophage polarization is a multifactorial process in which a huge number of factors can be involved producing different activation scenarios. Once a macrophage adopts a phenotype, it still retains the ability to continue changing in response to new environmental influences. The reversibility of polarization has a critical therapeutic value, especially in diseases in which an M1/M2 imbalance plays a pathogenic role. In this review, we assess the high plasticity of macrophages and their potential to be exploited to reduce chronic/detrimental inflammation. On the whole, the evidence detailed in this review underscores macrophage polarization as a target of interest for immunotherapy.
Topics: Animals; Autoimmune Diseases; Autoimmunity; Cytokines; Heme Oxygenase (Decyclizing); Humans; Immunoglobulins, Intravenous; Inflammation Mediators; Macrophage Activation; Macrophages; Phenotype
PubMed: 29455468
DOI: 10.1111/imm.12910