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Journal of Cellular Physiology Sep 2018Macrophages are heterogeneous and their phenotype and functions are regulated by the surrounding micro-environment. Macrophages commonly exist in two distinct subsets:... (Review)
Review
Macrophages are heterogeneous and their phenotype and functions are regulated by the surrounding micro-environment. Macrophages commonly exist in two distinct subsets: 1) Classically activated or M1 macrophages, which are pro-inflammatory and polarized by lipopolysaccharide (LPS) either alone or in association with Th1 cytokines such as IFN-γ, GM-CSF, and produce pro-inflammatory cytokines such as interleukin-1β (IL-1β), IL-6, IL-12, IL-23, and TNF-α; and 2) Alternatively activated or M2 macrophages, which are anti-inflammatory and immunoregulatory and polarized by Th2 cytokines such as IL-4 and IL-13 and produce anti-inflammatory cytokines such as IL-10 and TGF-β. M1 and M2 macrophages have different functions and transcriptional profiles. They have unique abilities by destroying pathogens or repair the inflammation-associated injury. It is known that M1/M2 macrophage balance polarization governs the fate of an organ in inflammation or injury. When the infection or inflammation is severe enough to affect an organ, macrophages first exhibit the M1 phenotype to release TNF-α, IL-1β, IL-12, and IL-23 against the stimulus. But, if M1 phase continues, it can cause tissue damage. Therefore, M2 macrophages secrete high amounts of IL-10 and TGF-β to suppress the inflammation, contribute to tissue repair, remodeling, vasculogenesis, and retain homeostasis. In this review, we first discuss the basic biology of macrophages including origin, differentiation and activation, tissue distribution, plasticity and polarization, migration, antigen presentation capacity, cytokine and chemokine production, metabolism, and involvement of microRNAs in macrophage polarization and function. Secondly, we discuss the protective and pathogenic role of the macrophage subsets in normal and pathological pregnancy, anti-microbial defense, anti-tumor immunity, metabolic disease and obesity, asthma and allergy, atherosclerosis, fibrosis, wound healing, and autoimmunity.
Topics: Animals; Cell Differentiation; Cytokines; Humans; Inflammation; Macrophages; Phenotype
PubMed: 29319160
DOI: 10.1002/jcp.26429 -
Immunity Mar 2016Inflammatory monocytes and tissue-resident macrophages are key regulators of tissue repair, regeneration, and fibrosis. After tissue injury, monocytes and macrophages... (Review)
Review
Inflammatory monocytes and tissue-resident macrophages are key regulators of tissue repair, regeneration, and fibrosis. After tissue injury, monocytes and macrophages undergo marked phenotypic and functional changes to play critical roles during the initiation, maintenance, and resolution phases of tissue repair. Disturbances in macrophage function can lead to aberrant repair, such that uncontrolled production of inflammatory mediators and growth factors, deficient generation of anti-inflammatory macrophages, or failed communication between macrophages and epithelial cells, endothelial cells, fibroblasts, and stem or tissue progenitor cells all contribute to a state of persistent injury, and this could lead to the development of pathological fibrosis. In this review, we discuss the mechanisms that instruct macrophages to adopt pro-inflammatory, pro-wound-healing, pro-fibrotic, anti-inflammatory, anti-fibrotic, pro-resolving, and tissue-regenerating phenotypes after injury, and we highlight how some of these mechanisms and macrophage activation states could be exploited therapeutically.
Topics: Animals; Cell Communication; Cell Differentiation; Fibrosis; Humans; Macrophage Activation; Macrophages; Phenotype; Regeneration; Wound Healing
PubMed: 26982353
DOI: 10.1016/j.immuni.2016.02.015 -
International Journal of Molecular... Dec 2021Macrophages are present in most human tissues and have very diverse functions. Activated macrophages are usually divided into two phenotypes, M1 macrophages and M2... (Review)
Review
Macrophages are present in most human tissues and have very diverse functions. Activated macrophages are usually divided into two phenotypes, M1 macrophages and M2 macrophages, which are altered by various factors such as microorganisms, tissue microenvironment, and cytokine signals. Macrophage polarity is very important for infections, inflammatory diseases, and malignancies; its management can be key in the prevention and treatment of diseases. In this review, we assess the current state of knowledge on macrophage polarity and report on its prospects as a therapeutic target.
Topics: Animals; Cell Polarity; Cytokines; Disease; Humans; Macrophages
PubMed: 35008577
DOI: 10.3390/ijms23010144 -
Immunity Sep 2022Single-cell and spatial transcriptomic technologies have revealed an underappreciated heterogeneity of liver macrophages. This has led us to rethink the involvement of... (Review)
Review
Single-cell and spatial transcriptomic technologies have revealed an underappreciated heterogeneity of liver macrophages. This has led us to rethink the involvement of macrophages in liver homeostasis and disease. Identification of conserved gene signatures within these cells across species and diseases is enabling the correct identification of specific macrophage subsets and the generation of more specific tools to track and study the functions of these cells. Here, we discuss what is currently known about the definitions of these different macrophage populations, the markers that can be used to identify them, how they are wired within the liver, and their functional specializations in health and disease.
Topics: Homeostasis; Kupffer Cells; Liver; Macrophages; Transcriptome
PubMed: 36103850
DOI: 10.1016/j.immuni.2022.08.002 -
Nature Jun 2023Embryo-derived tissue-resident macrophages are the first representatives of the haematopoietic lineage to emerge in metazoans. In mammals, resident macrophages originate... (Review)
Review
Embryo-derived tissue-resident macrophages are the first representatives of the haematopoietic lineage to emerge in metazoans. In mammals, resident macrophages originate from early yolk sac progenitors and are specified into tissue-specific subsets during organogenesis-establishing stable spatial and functional relationships with specialized tissue cells-and persist in adults. Resident macrophages are an integral part of tissues together with specialized cells: for instance, microglia reside with neurons in brain, osteoclasts reside with osteoblasts in bone, and fat-associated macrophages reside with white adipocytes in adipose tissue. This ancillary cell type, which is developmentally and functionally distinct from haematopoietic stem cell and monocyte-derived macrophages, senses and integrates local and systemic information to provide specialized tissue cells with the growth factors, nutrient recycling and waste removal that are critical for tissue growth, homeostasis and repair. Resident macrophages contribute to organogenesis, promote tissue regeneration following damage and contribute to tissue metabolism and defence against infectious disease. A correlate is that genetic or environment-driven resident macrophage dysfunction is a cause of degenerative, metabolic and possibly inflammatory and tumoural diseases. In this Review, we aim to provide a conceptual outline of our current understanding of macrophage physiology and its importance in human diseases, which may inform and serve the design of future studies.
Topics: Animals; Humans; Cell Differentiation; Cell Lineage; Hematopoietic Stem Cells; Macrophages; Microglia; Monocytes; Organ Specificity; Disease
PubMed: 37344646
DOI: 10.1038/s41586-023-06002-x -
Trends in Cell Biology Dec 2020Macrophages are cells of the innate immune system that regulate the maintenance of tissue homeostasis, host defense during pathogen infection, and tissue repair in... (Review)
Review
Macrophages are cells of the innate immune system that regulate the maintenance of tissue homeostasis, host defense during pathogen infection, and tissue repair in response to tissue injury. Recent studies indicate that macrophage functions are influenced by cellular metabolism, including lipid metabolism. Here, we review how macrophage lipid metabolism can be dynamically altered in different physiological and pathophysiological contexts and the key regulators involved. We also describe how alterations in lipid metabolism are integrated with the signaling pathways that specify macrophage functions, allowing for coordinated control of macrophage biology. Finally, we discuss how dysregulated lipid metabolism contributes to perturbed macrophage functions in settings such as atherosclerosis and pathogen infections.
Topics: Animals; Cholesterol; Energy Metabolism; Humans; Inflammation; Lipid Metabolism; Macrophages; Phagocytosis
PubMed: 33036870
DOI: 10.1016/j.tcb.2020.09.006 -
Immunity Jan 2023Metazoan tissue specification is associated with integration of macrophage lineage cells in sub-tissular niches to promote tissue development and homeostasis. Oncogenic... (Review)
Review
Metazoan tissue specification is associated with integration of macrophage lineage cells in sub-tissular niches to promote tissue development and homeostasis. Oncogenic transformation, most prevalently of epithelial cell lineages, results in maladaptation of resident tissue macrophage differentiation pathways to generate parenchymal and interstitial tumor-associated macrophages that largely foster cancer progression. In addition to growth factors, nutrients that can be consumed, stored, recycled, or converted to signaling molecules have emerged as crucial regulators of macrophage responses in tumor. Here, we review how nutrient acquisition through plasma membrane transporters and engulfment pathways control tumor-associated macrophage differentiation and function. We also discuss how nutrient metabolism regulates tumor-associated macrophages and how these processes may be targeted for cancer therapy.
Topics: Animals; Humans; Tumor-Associated Macrophages; Macrophages; Cell Differentiation; Neoplasms; Nutrients
PubMed: 36630912
DOI: 10.1016/j.immuni.2022.12.003 -
Immunological Reviews Nov 2014Macrophages are cellular components of the innate immune system that reside in virtually all tissues and contribute to immunity, repair, and homeostasis. The traditional... (Review)
Review
Macrophages are cellular components of the innate immune system that reside in virtually all tissues and contribute to immunity, repair, and homeostasis. The traditional view that all tissue-resident macrophages derive from the bone marrow through circulating monocyte intermediates has dramatically shifted recently with the observation that macrophages from embryonic progenitors can persist into adulthood and self-maintain by local proliferation. In several tissues, however, monocytes also contribute to the resident macrophage population, on which the local environment can impose tissue-specific macrophage functions. These observations have raised important questions: What determines resident macrophage identity and function, ontogeny or environment? How is macrophage proliferation regulated? In this review, we summarize the current knowledge about the identity, proliferation, and turnover of tissue-resident macrophages and how they differ from freshly recruited short-lived monocyte-derived cells. We examine whether macrophage proliferation can be qualified as self-renewal of mature differentiated cells and whether the concepts and molecular pathways are comparable to self-renewal mechanisms in stem cells. Finally, we discuss how improved understanding of macrophage identity and self-renewal could be exploited for therapeutic intervention of macrophage-mediated pathologies by selectively targeting freshly recruited or resident macrophages.
Topics: Animals; Cell Differentiation; Cell Proliferation; Humans; Macrophages; Organ Specificity; Phenotype
PubMed: 25319327
DOI: 10.1111/imr.12224 -
Frontiers in Immunology 2020The immunosuppressive status of the tumor microenvironment (TME) remains poorly defined due to a lack of understanding regarding the function of tumor-associated... (Review)
Review
The immunosuppressive status of the tumor microenvironment (TME) remains poorly defined due to a lack of understanding regarding the function of tumor-associated macrophages (TAMs), which are abundant in the TME. TAMs are crucial drivers of tumor progression, metastasis, and resistance to therapy. Intra- and inter-tumoral spatial heterogeneities are potential keys to understanding the relationships between subpopulations of TAMs and their functions. Antitumor M1-like and pro-tumor M2-like TAMs coexist within tumors, and the opposing effects of these M1/M2 subpopulations on tumors directly impact current strategies to improve antitumor immune responses. Recent studies have found significant differences among monocytes or macrophages from distinct tumors, and other investigations have explored the existence of diverse TAM subsets at the molecular level. In this review, we discuss emerging evidence highlighting the redefinition of TAM subpopulations and functions in the TME and the possibility of separating macrophage subsets with distinct functions into antitumor M1-like and pro-tumor M2-like TAMs during the development of tumors. Such redefinition may relate to the differential cellular origin and monocyte and macrophage plasticity or heterogeneity of TAMs, which all potentially impact macrophage biomarkers and our understanding of how the phenotypes of TAMs are dictated by their ontogeny, activation status, and localization. Therefore, the detailed landscape of TAMs must be deciphered with the integration of new technologies, such as multiplexed immunohistochemistry (mIHC), mass cytometry by time-of-flight (CyTOF), single-cell RNA-seq (scRNA-seq), spatial transcriptomics, and systems biology approaches, for analyses of the TME.
Topics: Animals; Cell Plasticity; Gene Expression Regulation, Neoplastic; Humans; Macrophages; Neoplasms; Phenotype; Signal Transduction; Transcriptome; Tumor Microenvironment
PubMed: 32849616
DOI: 10.3389/fimmu.2020.01731 -
Frontiers in Cellular and Infection... 2023(Mtb), the causative agent of Tuberculosis (TB), remains a pathogen of great interest on a global scale. This airborne pathogen affects the lungs, where it interacts... (Review)
Review
(Mtb), the causative agent of Tuberculosis (TB), remains a pathogen of great interest on a global scale. This airborne pathogen affects the lungs, where it interacts with macrophages. Acidic pH, oxidative and nitrosative stressors, and food restrictions make the macrophage's internal milieu unfriendly to foreign bodies. Mtb subverts the host immune system and causes infection due to its genetic arsenal and secreted effector proteins. and research have examined Mtb-host macrophage interaction. This interaction is a crucial stage in Mtb infection because lung macrophages are the first immune cells Mtb encounters in the host. This review summarizes Mtb effectors that interact with macrophages. It also examines how macrophages control and eliminate Mtb and how Mtb manipulates macrophage defense mechanisms for its own survival. Understanding these mechanisms is crucial for TB prevention, diagnosis, and treatment.
Topics: Humans; Mycobacterium tuberculosis; Macrophages; Tuberculosis; Macrophages, Alveolar; Lung; Host-Pathogen Interactions
PubMed: 36936766
DOI: 10.3389/fcimb.2023.1062963