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Frontiers in Cellular and Infection... 2020Monocytes and their derivatives, including macrophages and dendritic cells, play diverse roles in the response to fungal pathogens. Sensing of fungi by monocytes... (Review)
Review
Monocytes and their derivatives, including macrophages and dendritic cells, play diverse roles in the response to fungal pathogens. Sensing of fungi by monocytes triggers signaling pathways that mediate direct effects like phagocytosis and cytokine production. Monocytes can also present fungal antigens to elicit adaptive immune responses. These monocyte-mediated pathways may be either beneficial or harmful to the host. In some instances, fungi have developed mechanisms to evade the consequences of monocyte activation and subvert these cells to promote disease. Thus, monocytes are critically involved in mediating the outcomes of these often highly fatal infections. This review will highlight the roles of monocytes in the immune response to some of the major fungi that cause invasive human disease, including , and , and discuss potential strategies to manipulate monocyte responses in order to enhance anti-fungal immunity in susceptible hosts.
Topics: Antigens, Fungal; Fungi; Humans; Macrophages; Monocytes; Phagocytosis
PubMed: 32117808
DOI: 10.3389/fcimb.2020.00034 -
Biomedicine & Pharmacotherapy =... Sep 2023Mesenchymal stem cells (MSCs) are pluripotent stem cells derived from a variety of tissues, such as umbilical cord, fat, and bone marrow. Today, MSCs are widely... (Review)
Review
Mesenchymal stem cells (MSCs) are pluripotent stem cells derived from a variety of tissues, such as umbilical cord, fat, and bone marrow. Today, MSCs are widely recognized for their prominent anti-inflammatory properties in a variety of acute and chronic inflammatory diseases. In inflammatory diseases, monocytes/macrophages are an important part of the innate immune response in the body, and the alteration of the inflammatory phenotype plays a crucial role in the secretion of pro-inflammatory/anti-inflammatory factors, the repair of injured sites, and the infiltration of inflammatory cells. In this review, starting from the effect of MSCs on the monocyte/macrophage phenotype, we have outlined in detail the process by which MSCs influence the transformation of the monocyte/macrophage inflammatory phenotype, emphasizing the central role of monocytes/macrophages in MSC-mediated anti-inflammatory and damage site repair. MSCs are phagocytosed by monocytes/macrophages in various physiological states, the paracrine effect of MSCs and mitochondrial transfer of MSCs to macrophages to promote the transformation of monocytes/macrophages into anti-inflammatory phenotypes. We also review the clinical applications of the MSCs-monocytes/macrophages system and describe novel pathways between MSCs and tissue repair, the effects of MSCs on the adaptive immune system, and the effects of energy metabolism levels on monocyte/macrophage phenotypic changes.
Topics: Monocytes; Macrophages; Phenotype; Anti-Inflammatory Agents; Mesenchymal Stem Cells
PubMed: 37379639
DOI: 10.1016/j.biopha.2023.115042 -
International Journal of Molecular... Jul 2023Monocytes play a key role in the development of metabolic syndrome, and especially obesity. Given the complex features of their development from progenitor cells, whose... (Review)
Review
Monocytes play a key role in the development of metabolic syndrome, and especially obesity. Given the complex features of their development from progenitor cells, whose regulation is mediated by their interactions with bone marrow adipocytes, the importance of a detailed study of the heterogeneous composition of monocytes at the molecular and systemic levels becomes clear. Research argues for monocytes as indicators of changes in the body's metabolism and the possibility of developing therapeutic strategies to combat obesity and components of metabolic syndrome based on manipulations of the monocyte compound of the immune response. An in-depth study of the heterogeneity of bone-marrow-derived monocytes and adipocytes could provide answers to many questions about the pathogenesis of obesity and reveal their therapeutic potential.
Topics: Humans; Monocytes; Metabolic Syndrome; Adipocytes; Inflammation; Obesity
PubMed: 37569635
DOI: 10.3390/ijms241512259 -
Frontiers in Immunology 2020Monocytes are a highly plastic innate immune cell population that displays significant heterogeneity within the circulation. Distinct patterns of surface marker... (Review)
Review
Monocytes are a highly plastic innate immune cell population that displays significant heterogeneity within the circulation. Distinct patterns of surface marker expression have become accepted as a basis for distinguishing three monocyte subsets in humans. These phenotypic subsets, termed classical, intermediate and nonclassical, have also been demonstrated to differ in regard to their functional properties and disease associations when studied and . Nonetheless, for the intermediate monocyte subset in particular, functional experiments have yielded conflicting results and some studies point to further levels of heterogeneity. Developments in genetic sequencing technology have provided opportunities to more comprehensively explore the phenotypic and functional differences among conventionally-recognized immune cell subtypes as well as the potential to identify novel subpopulations. In this review, we summarize the transcriptomic evidence in support of the existence of three separate monocyte subsets. We also critically evaluate the insights into subset functional distinctions that have been garnered from monocyte gene expression analysis and the potential utility of such studies to unravel subset-specific functional changes which arise in disease states.
Topics: GPI-Linked Proteins; Gene Expression Profiling; Humans; Immune System Diseases; Immunity, Innate; Immunophenotyping; Lipopolysaccharide Receptors; Monocytes; Receptors, IgG
PubMed: 32582174
DOI: 10.3389/fimmu.2020.01070 -
Circulation Research Apr 2024While platelets have well-studied hemostatic functions, platelets are immune cells that circulate at the interface between the vascular wall and white blood cells. The...
BACKGROUND
While platelets have well-studied hemostatic functions, platelets are immune cells that circulate at the interface between the vascular wall and white blood cells. The physiological implications of these constant transient interactions are poorly understood. Activated platelets induce and amplify immune responses, but platelets may also maintain immune homeostasis in healthy conditions, including maintaining vascular integrity and T helper cell differentiation, meaning that platelets are central to both immune responses and immune quiescence. Clinical data have shown an association between low platelet counts (thrombocytopenia) and immune dysfunction in patients with sepsis and extracorporeal membrane oxygenation, further implicating platelets as more holistic immune regulators, but studies of platelet immune functions in nondisease contexts have had limited study.
METHODS
We used in vivo models of thrombocytopenia and in vitro models of platelet and monocyte interactions, as well as RNA-seq and ATAC-seq (assay for transposase-accessible chromatin with sequencing), to mechanistically determine how resting platelet and monocyte interactions immune program monocytes.
RESULTS
Circulating platelets and monocytes interact in a CD47-dependent manner to regulate monocyte metabolism, histone methylation, and gene expression. Resting platelet-monocyte interactions limit TLR (toll-like receptor) signaling responses in healthy conditions in an innate immune training-like manner. In both human patients with sepsis and mouse sepsis models, thrombocytopenia exacerbated monocyte immune dysfunction, including increased cytokine production.
CONCLUSIONS
Thrombocytopenia immune programs monocytes in a manner that may lead to immune dysfunction in the context of sepsis. This is the first demonstration that sterile, endogenous cell interactions between resting platelets and monocytes regulate monocyte metabolism and pathogen responses, demonstrating platelets to be immune rheostats in both health and disease.
Topics: Mice; Animals; Humans; Monocytes; Thrombocytopenia; Blood Platelets; Immunity; Sepsis; Platelet Activation
PubMed: 38456277
DOI: 10.1161/CIRCRESAHA.123.323662 -
Journal of Autoimmunity Nov 2023Systemic sclerosis (SSc) is a complex disease that affects the connective tissue, causing fibrosis. SSc patients show altered immune cell composition and activation in...
Systemic sclerosis (SSc) is a complex disease that affects the connective tissue, causing fibrosis. SSc patients show altered immune cell composition and activation in the peripheral blood (PB). PB monocytes (Mos) are recruited into tissues where they differentiate into macrophages, which are directly involved in fibrosis. To understand the role of CD14 PB Mos in SSc, a single-cell transcriptome analysis (scRNA-seq) was conducted on 8 SSc patients and 8 controls. Using unsupervised clustering methods, CD14 cells were assigned to 11 clusters, which added granularity to the known monocyte subsets: classical (cMos), intermediate (iMos) and non-classical Mos (ncMos) or type 2 dendritic cells. NcMos were significantly overrepresented in SSc patients and showed an active IFN-signature and increased expression levels of PTGES, in addition to monocyte motility and adhesion markers. We identified a SSc-related cluster of IRF7+ STAT1+ iMos with an aberrant IFN-response. Finally, a depletion of M2 polarised cMos in SSc was observed. Our results highlighted the potential of PB Mos as biomarkers for SSc and provided new possibilities for putative drug targets for modulating the innate immune response in SSc.
Topics: Humans; Scleroderma, Systemic; Monocytes; Interferons; Female; Male; Biomarkers; Middle Aged; Adult; Gene Expression Profiling; Single-Cell Analysis; Aged; Transcriptome; Lipopolysaccharide Receptors; Intramolecular Oxidoreductases
PubMed: 37633117
DOI: 10.1016/j.jaut.2023.103097 -
Proceedings of the Japan Academy.... 2023Inflammation is a host defense response to various invading stimuli, but an excessive and persistent inflammatory response can cause tissue injury, which can lead to... (Review)
Review
Inflammation is a host defense response to various invading stimuli, but an excessive and persistent inflammatory response can cause tissue injury, which can lead to irreversible organ damage and dysfunction. Excessive inflammatory responses are believed to link to most human diseases. A specific type of leukocyte infiltration into invaded tissues is required for inflammation. Historically, the underlying molecular mechanisms of this process during inflammation were an enigma, compromising research in the fields of inflammation, immunology, and pathology. However, the pioneering discovery of chemotactic cytokines (chemokines), monocyte-derived neutrophil chemotactic factor (MDNCF; interleukin [IL]-8, CXCL8) and monocyte chemotactic and activating factor (MCAF; monocyte chemotactic factor 1 [MCP-1], CCL2) in the late 1980s finally enabled us to address this issue. In this review, we provide a historical overview of chemokine research over the last 35 years.
Topics: Humans; Chemokine CCL2; Chemokines; Cytokines; Inflammation; Interleukin-8; Monocytes
PubMed: 37518010
DOI: 10.2183/pjab.99.014 -
Frontiers in Endocrinology 2022Obesity is associated with systemic inflammation and immune cell recruitment to metabolic tissues. Sex differences have been observed where male mice challenged with...
Obesity is associated with systemic inflammation and immune cell recruitment to metabolic tissues. Sex differences have been observed where male mice challenged with high fat diet (HFD) exhibit greater adipose tissue inflammation than females demonstrating a role for sex hormones in differential inflammatory responses. Circulating monocytes that respond to dietary lipids and chemokines and produce cytokines are the primary source of recruited adipose tissue macrophages (ATMs). In this study, we investigated sexual dimorphism in biological pathways in HFD-fed ATMs from male and female mice by RNA-seq. We also conducted chemotaxis assays to investigate sex differences in the migration of monocytes isolated from bone marrow from male and female mice toward a dietary saturated lipid - palmitate (PA), and a chemokine - monocyte chemoattractant protein 1 (MCP1), factors known to stimulate myeloid cells in obesity. ATM RNA-Seq demonstrated sex differences of both metabolic and inflammatory activation, including pathways for chemokine signaling and leukocyte trans-endothelial migration. monocyte transfer studies demonstrated that male monocytes traffic to female adipose tissue to generate ATMs more readily. In chemotaxis assays, lean male monocytes migrated in greater numbers than females toward PA and MCP1. With short-term HFD, male and female monocytes migrated similarly, but in chronic HFD, male monocytes showed greater migration than females upon PA and MCP1 stimulation. Studies with monocytes from toll-like receptor 4 knockout mice ( ) demonstrated that both males and females showed decreased migration than WT in response to PA and MCP1 implying a role for TLR4 in monocyte influx in response to meta-inflammation. Overall, these data demonstrate the role of sexual dimorphism in monocyte recruitment and response to metabolic stimuli that may influence meta-inflammation in obesity.
Topics: Animals; Female; Inflammation; Male; Mice; Mice, Inbred C57BL; Monocytes; Obesity; Sex Characteristics; Toll-Like Receptor 4
PubMed: 35422759
DOI: 10.3389/fendo.2022.826320 -
International Journal of Molecular... Jul 2021Monocytes (Mos) and macrophages (Mφs) are key players in the innate immune system and are critical in coordinating the initiation, expansion, and regression of many... (Review)
Review
Monocytes (Mos) and macrophages (Mφs) are key players in the innate immune system and are critical in coordinating the initiation, expansion, and regression of many autoimmune diseases. In addition, they display immunoregulatory effects that impact inflammation and are essential in tissue repair and regeneration. Juvenile idiopathic arthritis (JIA) is an umbrella term describing inflammatory joint diseases in children. Accumulated evidence suggests a link between Mo and Mφ activation and JIA pathogenesis. Accordingly, topics regarding the signals and mechanisms regulating Mo and Mφ activation leading to pathologies in patients with JIA are of great interest. In this review, we critically summarize recent advances in the understanding of how Mo and Mφ activation is involved in JIA pathogenesis and focus on the signaling pathways and mechanisms participating in the related cell activation processes.
Topics: Animals; Arthritis, Juvenile; Humans; Macrophage Activation; Macrophages; Monocytes; Signal Transduction
PubMed: 34360720
DOI: 10.3390/ijms22157960 -
International Journal of Molecular... Oct 2022Sjögren's syndrome is one of the most prevalent autoimmune diseases after rheumatoid arthritis, with a preference for middle age, and is characterised by exocrine... (Review)
Review
Sjögren's syndrome is one of the most prevalent autoimmune diseases after rheumatoid arthritis, with a preference for middle age, and is characterised by exocrine glandular involvement leading to xerostomia and xerophthalmia. It can have systemic implications with vascular, neurological, renal, and pulmonary involvement, and in some cases, it may evolve to non-Hodgkin's lymphoma. For a long time, B- and T-lymphocytes have been the focus of research and have been considered key players in Sjögren's syndrome pathogenesis and evolution. With the development of new technologies, including omics, more insights have been found on the different signalling pathways that lead to inflammation and activation of the immune system. New evidence indicates that a third actor linking innate and adaptive immunity plays a leading role in the Sjögren's syndrome play: the monocyte. This review summarises the recent insights from transcriptomic, proteomic, and epigenetic studies that help us to understand more about the Sjögren's syndrome pathophysiology and redefine the involvement of monocytes in this disease.
Topics: Middle Aged; Humans; Sjogren's Syndrome; Monocytes; Proteomics; Xerostomia; Xerophthalmia
PubMed: 36361554
DOI: 10.3390/ijms232112765