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Seminars in Immunology Oct 2016Macrophages are heterogeneous cells that play a key role in inflammatory and tissue reparative responses. Over the past decade it has become clear that shifts in... (Review)
Review
Macrophages are heterogeneous cells that play a key role in inflammatory and tissue reparative responses. Over the past decade it has become clear that shifts in cellular metabolism are important determinants of macrophage function and phenotype. At the same time, our appreciation of macrophage diversity in vivo has also been increasing. Factors such as cell origin and tissue localization are now recognized as important variables that influence macrophage biology. Whether different macrophage populations also have unique metabolic phenotypes has not been extensively explored. In this article, we will discuss the importance of understanding how macrophage origin can modulate metabolic programming and influence inflammatory responses.
Topics: Animals; Energy Metabolism; Gene Expression Regulation; Humans; Immunomodulation; Macrophage Activation; Macrophages; Metabolic Networks and Pathways; Organ Specificity; Phenotype
PubMed: 27771140
DOI: 10.1016/j.smim.2016.10.004 -
Inflammation Research : Official... Jan 2024Emerging studies have revealed that macrophages possess different dependences on the uptake, synthesis, and metabolism of serine for their activation and... (Review)
Review
OBJECTIVE
Emerging studies have revealed that macrophages possess different dependences on the uptake, synthesis, and metabolism of serine for their activation and functionalization, necessitating our insight into how serine availability and utilization impact macrophage activation and inflammatory responses.
METHODS
This article summarizes the reports published domestically and internationally about the serine uptake, synthesis, and metabolic flux by the macrophages polarizing with distinct stimuli and under different pathologic conditions, and particularly analyzes how altered serine metabolism rewires the metabolic behaviors of polarizing macrophages and their genetic and epigenetic reprogramming.
RESULTS
Macrophages dynamically change serine metabolism to orchestrate their anabolism, redox balance, mitochondrial function, epigenetics, and post-translation modification, and thus match the distinct needs for both classical and alternative activation.
CONCLUSION
Serine metabolism coordinates multiple metabolic pathways to tailor macrophage polarization and their responses to different pathogenic attacks and thus holds the potential as therapeutic target for types of acute and chronic inflammatory diseases.
Topics: Macrophage Activation; Macrophages; Metabolic Networks and Pathways; Epigenesis, Genetic
PubMed: 38070057
DOI: 10.1007/s00011-023-01815-y -
Frontiers in Immunology 2023Macrophages, as central components of innate immunity, feature significant heterogeneity. Numerus studies have revealed the pivotal roles of macrophages in the... (Review)
Review
Macrophages, as central components of innate immunity, feature significant heterogeneity. Numerus studies have revealed the pivotal roles of macrophages in the pathogenesis of liver fibrosis induced by various factors. Hepatic macrophages function to trigger inflammation in response to injury. They induce liver fibrosis by activating hepatic stellate cells (HSCs), and then inflammation and fibrosis are alleviated by the degradation of the extracellular matrix and release of anti-inflammatory cytokines. MicroRNAs (miRNAs), a class of small non-coding endogenous RNA molecules that regulate gene expression through translation repression or mRNA degradation, have distinct roles in modulating macrophage activation, polarization, tissue infiltration, and inflammation regression. Considering the complex etiology and pathogenesis of liver diseases, the role and mechanism of miRNAs and macrophages in liver fibrosis need to be further clarified. We first summarized the origin, phenotypes and functions of hepatic macrophages, then clarified the role of miRNAs in the polarization of macrophages. Finally, we comprehensively discussed the role of miRNAs and macrophages in the pathogenesis of liver fibrotic disease. Understanding the mechanism of hepatic macrophage heterogeneity in various types of liver fibrosis and the role of miRNAs on macrophage polarization provides a useful reference for further research on miRNA-mediated macrophage polarization in liver fibrosis, and also contributes to the development of new therapies targeting miRNA and macrophage subsets for liver fibrosis.
Topics: Humans; MicroRNAs; Macrophage Activation; Liver Cirrhosis; Liver Diseases; Macrophages; Inflammation
PubMed: 37138859
DOI: 10.3389/fimmu.2023.1147710 -
Seminars in Immunology Dec 2015Cellular activation is mainly defined as the response of a cell to exogenous signals eventually leading to changes in protein expression and cellular function.... (Review)
Review
Cellular activation is mainly defined as the response of a cell to exogenous signals eventually leading to changes in protein expression and cellular function. Originally, macrophage activation was mainly associated with phagocytic function. Later other effector functions such as cytokine secretion, upregulation of cell surface receptors came into focus. For a while macrophage activation was classified as being either pro-inflammatory or anti-inflammatory and certain signal transduction pathways were associated with these two conditions. Most recent findings on transcriptional and epigenetic level, however, suggest that the molecular features of macrophage activation are significantly more complex. Here, we will introduce a novel and integrative model of macrophage activation. Albeit recognizing that macrophage activation cannot be reduced to nuclear processes, we will focus in this review on the most recent findings concerning transcriptional and epigenetic regulation of macrophage activation. Understanding the complexity of the central regulatory mechanisms in the nucleus will form a foundation for deciphering all the different effector functions that are associated with macrophage activation.
Topics: Animals; Epigenesis, Genetic; Homeostasis; Humans; Inflammation; Macrophage Activation; Macrophages
PubMed: 27049460
DOI: 10.1016/j.smim.2016.03.009 -
EMBO Reports Sep 2021Macrophages react to microbial and endogenous danger signals by activating a broad panel of effector and homeostatic responses. Such responses entail rapid and... (Review)
Review
Macrophages react to microbial and endogenous danger signals by activating a broad panel of effector and homeostatic responses. Such responses entail rapid and stimulus-specific changes in gene expression programs accompanied by extensive rewiring of metabolism, with alterations in chromatin modifications providing one layer of integration of transcriptional and metabolic regulation. A systematic and mechanistic understanding of the mutual influences between signal-induced metabolic changes and gene expression is still lacking. Here, we discuss current evidence, controversies, knowledge gaps, and future areas of investigation on how metabolic and transcriptional changes are dynamically integrated during macrophage activation. The cross-talk between metabolism and inflammatory gene expression is in part accounted for by alterations in the production, usage, and availability of metabolic intermediates that impact the macrophage epigenome. In addition, stimulus-inducible gene expression changes alter the production of inflammatory mediators, such as nitric oxide, that in turn modulate the activity of metabolic enzymes thus determining complex regulatory loops. Critical issues remain to be understood, notably whether and how metabolic rewiring can bring about gene-specific (as opposed to global) expression changes.
Topics: Gene Expression; Gene Expression Regulation; Humans; Inflammation; Macrophage Activation; Macrophages
PubMed: 34328708
DOI: 10.15252/embr.202153251 -
Immunologic Research Apr 2023Macro-autophagy is a highly conserved catabolic process among eukaryotes affecting macrophages. This work studies the genetic regulatory network involving the interplay...
Macro-autophagy is a highly conserved catabolic process among eukaryotes affecting macrophages. This work studies the genetic regulatory network involving the interplay between autophagy and macrophage polarization (activation). Autophagy-related genes (Atgs) and differentially expressed genes (DEGs) of macrophage polarization (M1-M2) were predicted, and their regulatory networks constructed. Naïve (M0) mouse bone marrow-derived monocytes were differentiated into M1 and M2a. Validation of the targets of Smad1, LC3A and LC3B, Atg16L1, Atg7, IL-6, CD68, Arg-1, and Vamp7 was performed in vitro. Immunophenotyping by flow cytometry revealed three macrophage phenotypes: M0 (IL-6 + /CD68 +), M1 (IL-6 + /CD68 + /Arg-1 +), and M2a (CD68 + /Arg-1). Confocal microscopy revealed increased autophagy in both M1 and M2a and a significant increase in the pre-autophagosomes size and number. Bafilomycin A increased the expression of CD68 and Arg-1 in all cell lineages. In conclusion, our approach predicted the protein targets mediating the interplay between autophagy and macrophage polarization. We suggest that autophagy reprograms macrophage polarization via CD68, arginase 1, Atg16L1-1, and Atg16L1-3. The current findings provide a foundation for the future use of macrophages in immunotherapy of different autoimmune disorders.
Topics: Animals; Mice; Autophagy; Gene Regulatory Networks; Interleukin-6; Macrophage Activation; Macrophages; Monocytes
PubMed: 36451006
DOI: 10.1007/s12026-022-09344-2 -
Cellular & Molecular Biology Letters Oct 2022Macrophages are influential members of the innate immune system that can be reversibly polarized by different microenvironment signals. Cell polarization leads to a wide... (Review)
Review
Macrophages are influential members of the innate immune system that can be reversibly polarized by different microenvironment signals. Cell polarization leads to a wide range of features, involving the migration, development, and organization of the cells. There is mounting evidence that macrophage polarization plays a key role in the initiation and development of a wide range of diseases. This study aims to give an overview of macrophage polarization, their different subtypes, and the importance of alternatively activated M2 macrophage and classically activated M1 macrophage in immune responses and pathological conditions. This review provides insight on the role of exosomes in M1/M2-like macrophage polarization and their potential as a promising therapeutic candidate.
Topics: Exosomes; Immunity; Immunomodulation; Macrophage Activation; Macrophages
PubMed: 36192691
DOI: 10.1186/s11658-022-00384-y -
Immunology and Cell Biology Mar 2019Macrophages are a critical component of the innate immune response, and compose the first response to perturbations in tissue homeostasis. Their unique ability to... (Review)
Review
Macrophages are a critical component of the innate immune response, and compose the first response to perturbations in tissue homeostasis. Their unique ability to dynamically integrate diverse stimuli underlies their important role in the healing response from first insult to re-establishment of tissue homeostasis. While the roles of macrophages in tissue repair have been well-described in vitro and in vivo, the influence of cellular metabolism on macrophage function during tissue repair remains an unexplored area of immunometabolism. In this review, we will explore the unique metabolic requirements of inflammatory and anti-inflammatory macrophages and the potential contribution of macrophage metabolism to each phase of wound healing.
Topics: Animals; Biomarkers; Cellular Microenvironment; Disease Susceptibility; Energy Metabolism; Gene Expression Regulation; Homeostasis; Humans; Inflammation; Macrophage Activation; Macrophages; Metabolic Networks and Pathways; Signal Transduction; Wound Healing
PubMed: 30779212
DOI: 10.1111/imcb.12237 -
Naunyn-Schmiedeberg's Archives of... Jan 2022Macrophages are myeloid immune cells, present in virtually all tissues which exhibit considerable functional plasticity and diversity. Macrophages are often subdivided... (Review)
Review
Macrophages are myeloid immune cells, present in virtually all tissues which exhibit considerable functional plasticity and diversity. Macrophages are often subdivided into two distinct subsets described as classically activated (M1) and alternatively activated (M2) macrophages. It has recently emerged that metabolites regulate the polarization and function of macrophages by altering metabolic pathways. These metabolites often cannot freely pass the cell membrane and are therefore transported by the corresponding metabolite transporters. Here, we reviewed how glucose, glutamate, lactate, fatty acid, and amino acid transporters are involved in the regulation of macrophage polarization. Understanding the interactions among metabolites, metabolite transporters, and macrophage function under physiological and pathological conditions may provide further insights for novel drug targets for the treatment of macrophage-associated diseases. In Brief Recent studies have shown that the polarization and function of macrophages are regulated by metabolites, most of which cannot pass freely through biofilms. Therefore, metabolite transporters required for the uptake of metabolites have emerged seen as important regulators of macrophage polarization and may represent novel drug targets for the treatment of macrophage-associated diseases. Here, we summarize the role of metabolite transporters as regulators of macrophage polarization.
Topics: Animals; Cell Membrane; Humans; Macrophage Activation; Macrophages; Membrane Transport Proteins
PubMed: 34851450
DOI: 10.1007/s00210-021-02173-4 -
Nature Neuroscience Jun 2018Microglia differentiate from progenitors that infiltrate the nascent CNS during early embryonic development. They then remain in this unique immune-privileged... (Review)
Review
Microglia differentiate from progenitors that infiltrate the nascent CNS during early embryonic development. They then remain in this unique immune-privileged environment throughout life. Multiple immune mechanisms, which we collectively refer to as microglial checkpoints, ensure efficient and tightly regulated microglial responses to perturbations in the CNS milieu. Such mechanisms are essential for proper CNS development and optimal physiological function. However, in chronic disease or aging, when a robust immune response is required, such checkpoint mechanisms may limit the ability of microglia to protect the CNS. Here we survey microglial checkpoint mechanisms and their roles in controlling microglial function throughout life and in disease, and discuss how they may be targeted therapeutically.
Topics: Aging; Animals; Humans; Macrophage Activation; Microglia; Nervous System Diseases; T-Lymphocytes
PubMed: 29735982
DOI: 10.1038/s41593-018-0145-x