-
International Journal of Molecular... Jun 2022To date, four reviews and seven experimental articles have been published in this Special Issue [...].
To date, four reviews and seven experimental articles have been published in this Special Issue [...].
Topics: Macrophage Activation; Macrophages
PubMed: 35806211
DOI: 10.3390/ijms23137208 -
Cells Apr 2022MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression and thus act as important regulators of cellular phenotype and function. As their expression... (Review)
Review
MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression and thus act as important regulators of cellular phenotype and function. As their expression may be dysregulated in numerous diseases, they are of interest as biomarkers. What is more, attempts of modulation of some microRNAs for therapeutic reasons have been undertaken. In this review, we discuss the current knowledge regarding the influence of microRNAs on phagocytosis, which may be exerted on different levels, such as through macrophages polarization, phagosome maturation, reactive oxygen species production and cytokines synthesis. This phenomenon plays an important role in numerous pathological conditions.
Topics: Cytokines; Macrophage Activation; Macrophages; MicroRNAs; Phagocytosis
PubMed: 35563685
DOI: 10.3390/cells11091380 -
Journal of Immunology (Baltimore, Md. :... Feb 2023Macrophages are sentinels of the innate immune system that maintain tissue homeostasis and contribute to inflammatory responses. Their broad scope of action depends on... (Review)
Review
Macrophages are sentinels of the innate immune system that maintain tissue homeostasis and contribute to inflammatory responses. Their broad scope of action depends on both functional heterogeneity and plasticity. Small noncoding RNAs called microRNAs (miRNAs) contribute to macrophage function as post-transcriptional inhibitors of target gene networks. Genetic and pharmacologic studies have uncovered genes regulated by miRNAs that control macrophage cellular programming and macrophage-driven pathology. miRNAs control proinflammatory M1-like activation, immunoregulatory M2-like macrophage activation, and emerging macrophage functions in metabolic disease and innate immune memory. Understanding the gene networks regulated by individual miRNAs enhances our understanding of the spectrum of macrophage function at steady state and during responses to injury or pathogen invasion, with the potential to develop miRNA-based therapies. This review aims to consolidate past and current studies investigating the complexity of the miRNA interactome to provide the reader with a mechanistic view of how miRNAs shape macrophage behavior.
Topics: MicroRNAs; Macrophages; Gene Regulatory Networks; Macrophage Activation
PubMed: 36724439
DOI: 10.4049/jimmunol.2200467 -
Pflugers Archiv : European Journal of... Apr 2017Tissue macrophages and monocyte-derived macrophages are under continuous influence from environmental signals that define their activation status. Along these lines,... (Review)
Review
Tissue macrophages and monocyte-derived macrophages are under continuous influence from environmental signals that define their activation status. Along these lines, macrophages integrate tissue and stress signals and are specifically programmed by these signals towards a spectrum of functions necessary to fulfill their duty within their particular microenvironment, be it homeostatic tissue function, response to inflammatory pathophysiology, or even resolution of an inflammation. Recent years have seen tremendous progress in our understanding how macrophages at different sites are transcriptionally and epigenetically programmed to execute their diverse tasks throughout the body. The identification of transcription factors guiding these reprogramming activities is currently a major topic in macrophage research. We summarize the most recent findings within the last 18 months concerning the identification of novel transcription factors associated with particular macrophage location or function. Furthermore, we extend the view of cellular programming of macrophages to additional levels of regulation, for example, by long non-coding RNAs. Clearly, in addition to transcription factors, there are many more "programmers" shaping the versatile functionality of these exciting innate immune cells.
Topics: Animals; Homeostasis; Humans; Inflammation; Macrophage Activation; Macrophages; Transcription Factors
PubMed: 28185067
DOI: 10.1007/s00424-017-1943-9 -
Atherosclerosis Feb 2019Macrophages are key players in immunity and tissue homeostasis but can also contribute to a diverse range of human diseases, including cardiovascular diseases.... (Review)
Review
Macrophages are key players in immunity and tissue homeostasis but can also contribute to a diverse range of human diseases, including cardiovascular diseases. Enhancers, cis-acting DNA elements regulating gene activity, have been shown to be crucial for control of macrophage development and function. The selection and activities of macrophage-specific enhancers are regulated by the combined actions of lineage determining transcription factors (LDTFs) and signal dependent transcription factors (SDTFs) that are specified by developmental origin and tissue-specific signals. As a consequence, each tissue resident macrophage population adopts a distinct phenotype. In this review, we discuss recent work on how environmental factors affect the activation status of enhancers and can lead to long-lasting epigenetic changes resulting in innate immune memory. Furthermore, we discuss how non-coding genetic variation affects gene expression by altering transcription factor binding through local and domain-wide mechanisms. These findings have implications for interpretation of non-coding risk alleles that are associated with human disease and efforts to target macrophages for therapeutic purposes.
Topics: Animals; Cell Plasticity; Cellular Microenvironment; Epigenesis, Genetic; Gene-Environment Interaction; Humans; Immunity, Innate; Immunologic Memory; Macrophage Activation; Macrophages; Signal Transduction; Transcription, Genetic
PubMed: 30343819
DOI: 10.1016/j.atherosclerosis.2018.10.005 -
Proceedings of the National Academy of... Aug 2021Proinflammatory activation of macrophages in metabolic tissues is critically important in the induction of obesity-induced metaflammation. Here, we demonstrate that the...
Proinflammatory activation of macrophages in metabolic tissues is critically important in the induction of obesity-induced metaflammation. Here, we demonstrate that the soluble mannose receptor (sMR) plays a direct functional role in both macrophage activation and metaflammation. We show that sMR binds CD45 on macrophages and inhibits its phosphatase activity, leading to an Src/Akt/NF-κB-mediated cellular reprogramming toward an inflammatory phenotype both in vitro and in vivo. Remarkably, increased serum sMR levels were observed in obese mice and humans and directly correlated with body weight. Importantly, enhanced sMR levels increase serum proinflammatory cytokines, activate tissue macrophages, and promote insulin resistance. Altogether, our results reveal sMR as regulator of proinflammatory macrophage activation, which could constitute a therapeutic target for metaflammation and other hyperinflammatory diseases.
Topics: Animal Feed; Animals; Cells, Cultured; Cytokines; Diet, High-Fat; Gastrointestinal Microbiome; Gene Expression Regulation; Inflammation; Macrophage Activation; Macrophages; Male; Mannose Receptor; Membrane Proteins; Mice; Mice, Knockout; Random Allocation
PubMed: 34326259
DOI: 10.1073/pnas.2103304118 -
Immunity May 2017Recognition of pathogens by innate and adaptive immune cells instructs rapid alterations of cellular processes to promote effective resolution of infection. To... (Review)
Review
Recognition of pathogens by innate and adaptive immune cells instructs rapid alterations of cellular processes to promote effective resolution of infection. To accommodate increased bioenergetic and biosynthetic demands, metabolic pathways are harnessed to maximize proliferation and effector molecule production. In parallel, activation initiates context-specific gene-expression programs that drive effector functions and cell fates that correlate with changes in epigenetic landscapes. Many chromatin- and DNA-modifying enzymes make use of substrates and cofactors that are intermediates of metabolic pathways, providing potential cross talk between metabolism and epigenetic regulation of gene expression. In this review, we discuss recent studies of T cells and macrophages supporting a role for metabolic activity in integrating environmental signals with activation-induced gene-expression programs through modulation of the epigenome and speculate as to how this may influence context-specific macrophage and T cell responses to infection.
Topics: Animals; Cell Differentiation; Cellular Microenvironment; Energy Metabolism; Epigenesis, Genetic; Gene Expression Regulation; Humans; Immunity; Lymphocyte Activation; Macrophage Activation; Macrophages; Metabolic Networks and Pathways; T-Lymphocytes
PubMed: 28514673
DOI: 10.1016/j.immuni.2017.04.016 -
The Journal of Parasitology Dec 2014Despite recent advances in medical technology and a global effort to improve public health and hygiene, parasitic infections remain a major health and economic burden... (Review)
Review
Despite recent advances in medical technology and a global effort to improve public health and hygiene, parasitic infections remain a major health and economic burden worldwide. The World Health Organization estimates that about 1/3 of the world's population is currently infected with a soil-transmitted helminth, and millions more suffer from diseases caused by protozoan parasites including Plasmodium, Trypanosoma, and Leishmania species. Due to the selective pressure applied by parasitic and other infections, animals have evolved an intricate immune system; however, the current worldwide prevalence of parasitic infections clearly indicates that these pathogens have adapted equally well. Thus, developing a better understanding of the host-parasite relationship, particularly by focusing on the host immune response and the mechanisms by which parasites evade this response, is a critical first step in mitigating the detrimental effects of parasitic diseases. Macrophages are critical contributors during the host response to protozoan parasites, and the success or failure of these cells often tips the balance in favor of the host or parasite. Herein, we briefly discuss macrophage biology and provide an update on our current understanding of how these cells recognize glycosylphosphatidylinositol anchors from protozoan parasites as well as malarial hemozoin.
Topics: Animals; Glycosylphosphatidylinositols; Hemeproteins; Macrophage Activation; Macrophages; Phagocytosis; Plasmodium; Toll-Like Receptors
PubMed: 25265042
DOI: 10.1645/14-646.1 -
International Reviews of Immunology 2023Metabolic reprogramming is a hallmark of solid cancers. Macrophages as major constituents of immune system take important roles in regulation of tumorigenesis. Pro-tumor... (Review)
Review
Metabolic reprogramming is a hallmark of solid cancers. Macrophages as major constituents of immune system take important roles in regulation of tumorigenesis. Pro-tumor M2 macrophages preferentially use oxidative phosphorylation (OXPHOS) to meet their metabolic demands, while anti-tumor M1 macrophages use glycolysis as their dominant metabolic source. Dysregulation in metabolic systems is a driving force of skewing macrophages from M1 toward M2 phenotypical state. Hyperactive M1 macrophages, for instance, release metabolic products that are contributed to M2 macrophage polarization. Thus, metabolic remodeling through reinstating normalization in metabolic systems can be an effective tool in cancer therapy. The key focus of this review is over metabolic systems in macrophages and factors influencing their metabolic acquisition and reprogramming in cancer, as well as discussing bout strategies to adjust macrophage metabolism and reeducation toward M1-like phenotype.
Topics: Humans; Friends; Macrophages; Phenotype; Neoplasms; Macrophage Activation
PubMed: 35792727
DOI: 10.1080/08830185.2022.2095374 -
Cellular Microbiology Apr 2018Lysosomes are acidic and hydrolytic organelles responsible for receiving and digesting cargo acquired during endocytosis, phagocytosis, and autophagy. For macrophages... (Review)
Review
Lysosomes are acidic and hydrolytic organelles responsible for receiving and digesting cargo acquired during endocytosis, phagocytosis, and autophagy. For macrophages and dendritic cells, the lysosome is kingpin, playing a direct role in microbe killing and antigen processing for presentation. Strikingly, the historic view that lysosomes are homogeneous and static organelles is being replaced with a more elegant paradigm, in which lysosomes are heterogeneous, dynamic, and respond to cellular needs. For example, lysosomes are signalling platforms that integrate stress detection and molecular decision hubs such as the mTOR complex 1 and AMPK to modulate cellular activity. These signals can even adjust lysosome activity by modulating transcription factors such as transcription factor EB (TFEB) and TFE3 that govern lysosome gene expression. Here, we review lysosome remodelling and adaptation during macrophage and dendritic cell stimulation. First, we assess the functional outcomes and regulatory mechanisms driving the dramatic restructuring of lysosomes from globular organelles into a tubular network during phagocyte activation. Second, we discuss lysosome adaptation and scaling in macrophages driven by TFEB and TFE3 stimulation in response to phagocytosis and microbe challenges. Collectively, we are beginning to appreciate that lysosomes are dynamic and adapt to serve phagocyte differentiation in response to microbes and immune stress.
Topics: Animals; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Dendritic Cells; Humans; Lysosomes; Macrophage Activation; Macrophages; Phagocytosis
PubMed: 29349904
DOI: 10.1111/cmi.12824