G-CSF – A double edge sword in neutrophil mediated immunity

Seminars in Immunology, Journal Year: 2021, Volume and Issue: 54, P. 101516 - 101516

Published: April 1, 2021

Language: Английский

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Neutrophil Extracellular Traps (NETs) in Severe SARS-CoV-2 Lung Disease

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(16), P. 8854 - 8854

Published: Aug. 17, 2021

Neutrophil extracellular traps (NETs), built from mitochondrial or nuclear DNA, proteinases, and histones, entrap eliminate pathogens in the course of bacterial viral infections. Neutrophils’ activation formation NETs have been described as major risk factors for acute lung injury, multi-organ damage, mortality COVID-19 disease. NETs-related injury involves both epithelial endothelial cells, well alveolar-capillary barrier. The markers formation, such circulating neutrophil elastase (NE) activity, myeloperoxidase-DNA complexes, were found specimens victims, sera tracheal aspirates obtained patients. DNA threads form large conglomerates causing local obstruction small bronchi together with NE are responsible overproduction mucin by cells. Various components involved pathogenesis cytokine storm SARS-CoV-2 pulmonary interplay between inflammation thrombosis affected lungs. immunothrombosis, stimulated NETs, has a poor prognostic significance. Better understanding role can help to develop novel approaches therapeutic interventions this condition.

Language: Английский

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SARS-CoV-2 causes senescence in human cells and exacerbates the senescence-associated secretory phenotype through TLR-3

Aging, Journal Year: 2021, Volume and Issue: 13(18), P. 21838 - 21854

Published: Sept. 16, 2021

Aging | doi:10.18632/aging.203560. Utkarsh Tripathi, Rayhane Nchioua, Larissa G. P. Langhi Prata, Yi Zhu, Erin O. Wissler Gerdes, Nino Giorgadze, Tamar Pirtskhalava, Erik Parker, Ailing Xue, Jair Machado Espindola-Netto, Steffen Stenger, Paul D. Robbins, Laura J. Niedernhofer, Stephanie L. Dickinson, David B. Allison, Frank Kirchhoff, Konstantin Maria Johannes Sparrer, Tchkonia, James Kirkland

Language: Английский

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Metoprolol in Critically Ill Patients With COVID-19

Journal of the American College of Cardiology, Journal Year: 2021, Volume and Issue: 78(10), P. 1001 - 1011

Published: Aug. 30, 2021

Severe coronavirus disease-2019 (COVID-19) can progress to an acute respiratory distress syndrome (ARDS), which involves alveolar infiltration by activated neutrophils. The beta-blocker metoprolol has been shown ameliorate exacerbated inflammation in the myocardial infarction setting. purpose of this study was evaluate effects on and function patients with COVID-19–associated ARDS. A total 20 COVID-19 ARDS invasive mechanical ventilation were randomized (15 mg daily for 3 days) or control (no treatment). All underwent bronchoalveolar lavage (BAL) before after metoprolol/control. safety administration evaluated hemodynamic electrocardiogram monitoring echocardiography. Metoprolol without side effects. At baseline, neutrophil content BAL did not differ between groups. Conversely, had significantly fewer neutrophils day 4 (median: 14.3 neutrophils/µl [Q1, Q3: 4.63, 265 neutrophils/µl] vs median: 397 222, 1,346 groups, respectively; P = 0.016). also reduced extracellular traps other markers lung inflammation. Oxygenation (PaO2:FiO2) improved days treatment 130 110, 162] 267 199, 298] at baseline 4, 0.003), whereas it remained unchanged subjects. Metoprolol-treated spent than those group (15.5 ± 7.6 21.9 12.6 days; 0.17). In pilot trial, intravenous safe, inflammation, oxygenation. Repurposing appears be a safe inexpensive strategy that alleviate burden pandemic.

Language: Английский

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Viral and Bacterial Co-Infections in the Lungs: Dangerous Liaisons

Viruses, Journal Year: 2021, Volume and Issue: 13(9), P. 1725 - 1725

Published: Aug. 30, 2021

Respiratory tract infections constitute a significant public health problem, with therapeutic arsenal that remains relatively limited and is threatened by the emergence of antiviral and/or antibiotic resistance. Viral-bacterial co-infections are very often associated severity these respiratory have been explored mainly in context bacterial superinfections following primary influenza infection. This review summarizes our current knowledge mechanisms underlying between viruses (influenza viruses, RSV, SARS-CoV-2) bacteria, at both physiological immunological levels. also explores importance microbiome pathological evolution presents different vitro vivo experimental models available. A better understanding complex functional interactions viruses/bacteria host cells will allow development new, specific, more effective diagnostic approaches.

Language: Английский

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Neurotropism of SARS-CoV-2 and neurological diseases of the central nervous system in COVID-19 patients

Experimental Brain Research, Journal Year: 2021, Volume and Issue: 240(1), P. 9 - 25

Published: Oct. 25, 2021

Language: Английский

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Metabolic reprograming shapes neutrophil functions in severe COVID‐19

European Journal of Immunology, Journal Year: 2021, Volume and Issue: 52(3), P. 484 - 502

Published: Dec. 6, 2021

To better understand the mechanisms at basis of neutrophil functions during SARS-CoV-2, we studied patients with severe COVID-19 pneumonia. They had high blood proportion degranulated neutrophils and elevated plasma levels myeloperoxidase (MPO), elastase, MPO-DNA complexes, which are typical markers extracellular traps (NET). Their display dysfunctional mitochondria, defective oxidative burst, increased glycolysis, glycogen accumulation in cytoplasm, increase glycogenolysis. Hypoxia-inducible factor 1α (ΗΙF-1α) is stabilized such cells, it controls level phosphorylase L (PYGL), a key enzyme Inhibiting PYGL abolishes ability to produce NET. Patients displayed significant increases molecules involved regulation neutrophils' function including CCL2, CXCL10, CCL20, IL-18, IL-3, IL-6, G-CSF, GM-CSF, IFN-γ. Our data suggest that metabolic remodelling vital for formation NET boosting inflammatory response, thus, suggesting modulating ΗΙF-1α or could represent novel approach innovative therapies.

Language: Английский

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Rapid Protection from COVID-19 in Nonhuman Primates Vaccinated Intramuscularly but Not Intranasally with a Single Dose of a Vesicular Stomatitis Virus-Based Vaccine

mBio, Journal Year: 2022, Volume and Issue: 13(1)

Published: Jan. 11, 2022

The vesicular stomatitis virus (VSV) vaccine platform rose to fame in 2019, when a VSV-based Ebola (EBOV) was approved by the European Medicines Agency and U.S. Food Drug Administration for human use against deadly disease.

Language: Английский

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Diagnosis and Prognosis of COVID-19 Disease Using Routine Blood Values and LogNNet Neural Network

Sensors, Journal Year: 2022, Volume and Issue: 22(13), P. 4820 - 4820

Published: June 25, 2022

Since February 2020, the world has been engaged in an intense struggle with COVID-19 dis-ease, and health systems have come under tragic pressure as disease turned into a pandemic. The aim of this study is to obtain most effective routine blood values (RBV) diagnosis prognosis using backward feature elimination algorithm for LogNNet reservoir neural network. first dataset consists total 5296 patients same number negative positive tests. LogNNet-model achieved accuracy rate 99.5% 46 features 99.17% only mean corpuscular hemoglobin concentration, hemoglobin, activated partial prothrombin time. second 3899 who were treated hospital, which 203 severe 3696 mild patients. model reached 94.4% determining 48 82.7% erythrocyte sedimentation rate, neutrophil count, C reactive protein features. Our method will reduce pressures on sector help doctors understand pathogenesis key promising create mobile monitoring Internet Things.

Language: Английский

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Key benefits of dexamethasone and antibody treatment in COVID-19 hamster models revealed by single-cell transcriptomics

Molecular Therapy, Journal Year: 2022, Volume and Issue: 30(5), P. 1952 - 1965

Published: March 24, 2022

For coronavirus disease 2019 (COVID-19), effective and well-understood treatment options are still scarce. Since vaccine efficacy is challenged by novel variants, short-lasting immunity, hesitancy, understanding optimizing therapeutic remains essential. We aimed at better the effects of two standard-of-care drugs, dexamethasone anti-severe acute respiratory syndrome 2 (SARS-CoV-2) antibodies, on infection host responses. By using COVID-19 hamster models, pulmonary immune responses were analyzed to characterize single or combinatorial treatments. Pulmonary viral burden was reduced anti-SARS-CoV-2 antibody unaltered increased alone. Dexamethasone exhibited strong anti-inflammatory prevented fulminant in a severe model. Combination therapy showed additive benefits with both anti-viral potency. Bulk single-cell transcriptomic analyses confirmed dampened inflammatory cell recruitment into lungs upon identified specifically responsive subpopulation neutrophils, thereby indicating potential mechanism action. Our confirm properties suggest possible mechanisms, validate treatment, reveal synergistic combination therapy, thus informing more therapies.

Language: Английский

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