Neutrophils in COVID-19: recent insights and advances

Virology Journal, Journal Year: 2023, Volume and Issue: 20(1)

Published: Aug. 2, 2023

Abstract Coronavirus disease 2019 (COVID-19) is an acute respiratory caused by severe syndrome coronavirus 2 (SARS-CoV-2), which can lead to distress (ARDS), multi-organ failure and death, posing significant threat human health. Studies have found that pathological mechanisms, such as cytokine storms uncontrolled innate immune system activation, release of damage-associated molecular patterns during tissue injury a high incidence thrombotic events, are associated with the function dysfunction neutrophils. Specifically, increased formation low-density neutrophils (LDNs) neutrophil extracellular traps (NETs) has been shown be closely linked severity poor prognosis in patients COVID-19. Our work focuses on understanding number, abnormal lung infiltration, elevated neutrophil-to-lymphocyte ratio pathogenesis We also explore involvement NETs LDNs progression thrombosis formation, along potential therapeutic strategies targeting formation.

Language: Английский

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Pathophysiological mechanisms of thrombosis in acute and long COVID-19

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Nov. 16, 2022

COVID-19 patients have a high incidence of thrombosis, and thromboembolic complications are associated with severe mortality. disease is hyper-inflammatory response (cytokine storm) mediated by the immune system. However, role inflammatory in thrombosis remains incompletely understood. In this review, we investigate crosstalk between inflammation context COVID-19, focusing on contributions to pathogenesis propose combined use anti-inflammatory anticoagulant therapeutics. Under conditions, interactions neutrophils platelets, platelet activation, monocyte tissue factor expression, microparticle release, phosphatidylserine (PS) externalization as well complement activation collectively involved immune-thrombosis. Inflammation results apoptosis blood cells, leading release PS cells microparticles, which significantly enhances catalytic efficiency tenase prothrombinase complexes, promotes thrombin-mediated fibrin generation local clot formation. Given risk importance antithrombotic therapies has been generally recognized, but certain deficiencies treatment gaps remain. Antiplatelet drugs not combination treatments, thus fail dampen procoagulant activity. Current treatments also do an optimal time for anticoagulation. The efficacy depends therapy initiation. best early possible after diagnosis, ideally stage disease. We elaborate mechanisms long COVID complications, including persistent inflammation, endothelial injury dysfunction, coagulation abnormalities. above-mentioned contents provide therapeutic strategies further improve patient outcomes.

Language: Английский

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New Perspectives on the Importance of Cell-Free DNA Biology

Diagnostics, Journal Year: 2022, Volume and Issue: 12(9), P. 2147 - 2147

Published: Sept. 3, 2022

Body fluids are constantly replenished with a population of genetically diverse cell-free DNA (cfDNA) fragments, representing vast reservoir information reflecting real-time changes in the host and metagenome. As many body can be collected non-invasively one-off serial fashion, this tapped to develop assays for diagnosis, prognosis, monitoring wide-ranging pathologies, such as solid tumors, fetal genetic abnormalities, rejected organ transplants, infections, potentially others. The translation cfDNA research into useful clinical tests is gaining momentum, recent progress being driven by rapidly evolving preanalytical analytical procedures, integrated bioinformatics, machine learning algorithms. Yet, despite these spectacular advances, remains very challenging analyte due its immense heterogeneity fluctuation vivo. It increasingly recognized that high-fidelity reconstruction stored cfDNA, turn development fit roll-out, requires much deeper understanding both physico-chemical features biological, physiological, lifestyle, environmental factors modulate it. This daunting task, but significant upsides. In review we showed how expanded knowledge on biology faithful reverse-engineering samples promises (i) augment sensitivity specificity existing assays; (ii) expand repertoire disease-specific markers, thereby leading powerful (iii) reshape personal molecular medicine; (iv) have an unprecedented impact genetics research.

Language: Английский

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Neutrophil profiles of pediatric COVID-19 and multisystem inflammatory syndrome in children

Cell Reports Medicine, Journal Year: 2022, Volume and Issue: 3(12), P. 100848 - 100848

Published: Nov. 21, 2022

Multisystem inflammatory syndrome in children (MIS-C) is a delayed-onset, COVID-19-related hyperinflammatory illness characterized by severe acute respiratory coronavirus 2 (SARS-CoV-2) antigenemia, cytokine storm, and immune dysregulation. In COVID-19, neutrophil activation central to complications, yet the role of neutrophils MIS-C undefined. Here, we collect blood from 152 children: 31 cases MIS-C, 43 pediatric 78 controls. We find that display granulocytic myeloid-derived suppressor cell (G-MDSC) signature with highly altered metabolism distinct interferon-stimulated gene (ISG) response observe COVID-19. Moreover, extensive spontaneous extracellular trap (NET) formation identify degranulation signatures. Mechanistically, determine SARS-CoV-2 complexes are sufficient trigger NETosis. Our findings suggest presentation during could be mechanistically linked persistent driven uncontrolled NET release vasculature.

Language: Английский

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Role and Therapeutic Targeting Strategies of Neutrophil Extracellular Traps in Inflammation

International Journal of Nanomedicine, Journal Year: 2023, Volume and Issue: Volume 18, P. 5265 - 5287

Published: Sept. 1, 2023

Abstract: Neutrophil extracellular traps (NETs) are large DNA reticular structures secreted by neutrophils and decorated with histones antimicrobial proteins. As a key mechanism for to resist microbial invasion, NETs play an important role in the killing of microorganisms (bacteria, fungi, viruses). Although mostly known mediating killing, increasing evidence suggests that excessive induced stimulation physical chemical components, microorganisms, pathological factors can exacerbate inflammation organ damage. This review summarizes induction focuses on strategies inhibiting NETosis mechanisms involved pathogen evasion NETs. Furthermore, herbal medicine inhibitors nanodelivery improve efficiency inhibition levels Graphical Keywords: neutrophil traps, inflammation, targeted inhibition, nanotherapy,

Language: Английский

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Neutrophil diversity and function in health and disease

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Dec. 5, 2024

Abstract Neutrophils, the most abundant type of granulocyte, are widely recognized as one pivotal contributors to acute inflammatory response. Initially, neutrophils were considered mobile infantry innate immune system, tasked with immediate response invading pathogens. However, recent studies have demonstrated that versatile cells, capable regulating various biological processes and impacting both human health disease. Cytokines other active mediators regulate functional activity by activating multiple receptors on these thereby initiating downstream signal transduction pathways. Dysfunctions in disruptions neutrophil homeostasis been implicated pathogenesis numerous diseases, including cancer disorders, often due aberrant intracellular signaling. This review provides a comprehensive synthesis functions, integrating advancements this field. Moreover, it examines roles signaling pathways involved regulation activity. The pathophysiology diseases emerging therapeutic approaches targeting them also elaborated. addresses current limitations within field research, highlighting critical gaps knowledge warrant further investigation. In summary, seeks establish multidimensional model regulation, providing new perspectives for potential clinical applications research.

Language: Английский

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Butyrate: Connecting the gut-lung axis to the management of pulmonary disorders

Frontiers in Nutrition, Journal Year: 2022, Volume and Issue: 9

Published: Oct. 20, 2022

Short-chain fatty acids (SCFAs) are metabolites released by bacterial components of the microbiota. These molecules have a wide range effects in microbiota itself, but also host cells which they known for contributing to regulation cell metabolism, barrier function, and immunological responses. Recent studies indicate that these important players gut-lung axis highlight possibility using strategies alter their intestinal production prevent or treat distinct lung inflammatory diseases. Here, we review SCFA butyrate its derivatives vitro vivo on murine models respiratory disorders, besides discussing potential therapeutic use other SCFAs

Language: Английский

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Mechanisms of COVID-19 Associated Pulmonary Thrombosis: A Narrative Review

Biomedicines, Journal Year: 2023, Volume and Issue: 11(3), P. 929 - 929

Published: March 16, 2023

COVID-19, the infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is frequently associated with pulmonary thrombotic events, especially in hospitalized patients. Severe SARS-CoV-2 infection characterized a proinflammatory state and an disbalance hemostasis. Immune pathology analysis supports inflammatory nature of arterial thrombi composed white blood cells, neutrophils, CD3+ CD20+ lymphocytes, fibrin, red platelets. cytokines, chemokines, complement system are key drivers immunothrombosis, as they induce damage endothelial cells initiate procoagulant positive feedback loops. Neutrophil extracellular traps induced COVID-19-associated “cytokine storm”, platelets, coagulation pathways close inflammation–endotheliopathy–thrombosis axis, contributing to SARS-CoV-2-associated events. The hypothesis immunothrombosis also supported minor role venous thromboembolism chest CT imaging data showing peripheral clots lesions high incidence events despite routine thromboprophylaxis. Understanding complex mechanisms behind COVID-19-induced thrombosis will lead future combination therapies for patients that would target crossroads pathways.

Language: Английский

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Neutrophil-derived Activin-A moderates their pro-NETotic activity and attenuates collateral tissue damage caused by Influenza A virus infection

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 26, 2024

Background Pre-neutrophils, while developing in the bone marrow, transcribe Inhba gene and synthesize Activin-A protein, which they store release at earliest stage of their activation periphery. However, role neutrophil-derived is not completely understood. Methods To address this issue, we developed a neutrophil-specific Activin-A-deficient animal model ( S100a8-Cre/Inhba fl/fl mice) analyzed immune response to Influenza A virus (IAV) infection. More specifically, evaluation body weight lung mechanics, molecular cellular analyses bronchoalveolar lavage fluids, flow cytometry cell sorting cells, as well histopathological analysis tissues, were performed PBS-treated IAV-infected transgenic animals. Results We found that deficiency led exacerbated pulmonary inflammation widespread hemorrhagic histopathology lungs animals was associated with an exuberant production neutrophil extracellular traps (NETs). Moreover, deletion receptor ALK4/ACVR1B neutrophils IAV-induced pathology well, suggesting themselves are potential targets Activin-A-mediated signaling. The pro-NETotic tendency further verified context thioglycollate-induced peritonitis, characterized by robust peritoneal neutrophilia. Of importance, transcriptome revealed alterations consistent predisposition for NET release. Conclusion Collectively, our data demonstrate Activin-A, secreted upon periphery, acts feedback mechanism moderate limit collateral tissue damage caused excess during inflammatory response.

Language: Английский

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Association of vascular netosis with COVID-19 severity in asymptomatic and symptomatic patients

iScience, Journal Year: 2024, Volume and Issue: 27(5), P. 109573 - 109573

Published: March 26, 2024

Language: Английский

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