-
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 -
Immunity Jul 2014Description of macrophage activation is currently contentious and confusing. Like the biblical Tower of Babel, macrophage activation encompasses a panoply of descriptors...
Description of macrophage activation is currently contentious and confusing. Like the biblical Tower of Babel, macrophage activation encompasses a panoply of descriptors used in different ways. The lack of consensus on how to define macrophage activation in experiments in vitro and in vivo impedes progress in multiple ways, including the fact that many researchers still consider there to be only two types of activated macrophages, often termed M1 and M2. Here, we describe a set of standards encompassing three principles-the source of macrophages, definition of the activators, and a consensus collection of markers to describe macrophage activation-with the goal of unifying experimental standards for diverse experimental scenarios. Collectively, we propose a common framework for macrophage-activation nomenclature.
Topics: Animals; Granulocyte-Macrophage Colony-Stimulating Factor; Guidelines as Topic; Humans; Macrophage Activation; Macrophage Colony-Stimulating Factor; Macrophages; Mice; Research; Terminology as Topic
PubMed: 25035950
DOI: 10.1016/j.immuni.2014.06.008 -
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 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 -
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 -
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 -
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 -
Frontiers in Immunology 2019Macrophages are a heterogeneous population of immune cells playing several and diverse functions in homeostatic and immune responses. The broad spectrum of macrophage... (Review)
Review
Macrophages are a heterogeneous population of immune cells playing several and diverse functions in homeostatic and immune responses. The broad spectrum of macrophage functions depends on both heterogeneity and plasticity of these cells, which are highly specialized in sensing the microenvironment and modify their properties accordingly. Although it is clear that macrophage phenotypes are difficult to categorize and should be seen as plastic and adaptable, they can be simplified into two extremes: a pro-inflammatory (M1) and an anti-inflammatory/pro-resolving (M2) profile. Based on this definition, M1 macrophages are able to start and sustain inflammatory responses, secreting pro-inflammatory cytokines, activating endothelial cells, and inducing the recruitment of other immune cells into the inflamed tissue; on the other hand, M2 macrophages promote the resolution of inflammation, phagocytose apoptotic cells, drive collagen deposition, coordinate tissue integrity, and release anti-inflammatory mediators. Dramatic switches in cell metabolism accompany these phenotypic and functional changes of macrophages. In particular, M1 macrophages rely mainly on glycolysis and present two breaks on the TCA cycle that result in accumulation of itaconate (a microbicide compound) and succinate. Excess of succinate leads to Hypoxia Inducible Factor 1α (HIF1α) stabilization that, in turn, activates the transcription of glycolytic genes, thus sustaining the glycolytic metabolism of M1 macrophages. On the contrary, M2 cells are more dependent on oxidative phosphorylation (OXPHOS), their TCA cycle is intact and provides the substrates for the complexes of the electron transport chain (ETC). Moreover, pro- and anti-inflammatory macrophages are characterized by specific pathways that regulate the metabolism of lipids and amino acids and affect their responses. All these metabolic adaptations are functional to support macrophage activities as well as to sustain their polarization in specific contexts. The aim of this review is to discuss recent findings linking macrophage functions and metabolism.
Topics: Citric Acid Cycle; Glycolysis; Humans; Inflammation; Macrophage Activation; Macrophages; Oxidation-Reduction; Oxidative Phosphorylation
PubMed: 31333642
DOI: 10.3389/fimmu.2019.01462 -
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 2022Iron is a critical element for living cells in terrestrial life. Although iron metabolism is strictly controlled in the body, disturbance of iron homeostasis under... (Review)
Review
Iron is a critical element for living cells in terrestrial life. Although iron metabolism is strictly controlled in the body, disturbance of iron homeostasis under certain type of condition leads to innate and adaptive immune response. In innate immunity, iron regulates macrophage polarizations, neutrophils recruitment, and NK cells activity. In adaptive immunity, iron had an effect on the activation and differentiation of Th1, Th2, and Th17 and CTL, and antibody response in B cells. In this review, we focused on iron and immune regulation and listed the specific role of iron in macrophage polarization, T-cell activation, and B-cells antibody response. In addition, correlations between iron and several diseases such as cancer and aging degenerative diseases and some therapeutic strategies targeting those diseases are also discussed.
Topics: Adaptive Immunity; Immunity, Innate; Iron; Lymphocyte Activation; Macrophage Activation
PubMed: 35401569
DOI: 10.3389/fimmu.2022.816282