Innate immunological pathways in COVID-19 pathogenesis

Science Immunology, Journal Year: 2022, Volume and Issue: 7(67)

Published: Jan. 7, 2022

Coronavirus disease 2019 (COVID-19) is a characterized by profound dysregulation of the innate immune system. This knowledge has emerged from large body single-cell omics studies patients with COVID-19, which have provided one most detailed cellular atlases human ever. However, we are only beginning to understand immunological pathways that govern host defense and immunopathology in COVID-19. In this review, discuss emerging understanding how SARS-CoV-2 host-derived molecules activate specific pattern recognition receptors elicit protective interferon responses pathological cytokine responses, particular focus on acute infection lung pathophysiology critical addition, these modulated virus-host interactions stress-sensing pathways. In-depth mechanisms will likely uncover molecular targets for treatment COVID-19 other viral infections. it reveal fine balance between beneficial versus causing responses.

Language: Английский

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The Role of Cytokines and Chemokines in Severe Acute Respiratory Syndrome Coronavirus 2 Infections

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

Published: April 7, 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in countless infections and caused millions of deaths since its emergence 2019. Coronavirus disease 2019 (COVID-19)-associated mortality is by uncontrolled inflammation, aberrant immune response, cytokine storm, an imbalanced hyperactive system. The storm further results multiple organ failure lung immunopathology. Therefore, any potential treatments should focus on the direct elimination viral particles, prevention strategies, mitigation (hyperactive) This review focuses secretions innate adaptive responses against COVID-19, including interleukins, interferons, tumor necrosis factor-alpha, other chemokines. In addition to focus, we discuss immunotherapeutic approaches based relevant pathophysiological features, systemic response SARS-CoV-2, data from recent clinical trials experiments COVID-19-associated storm. Prompt use these cytokines as diagnostic markers aggressive management can help determine morbidity mortality. prophylaxis rapid appear significantly improve outcomes. For reasons, this study aims provide advanced information facilitate innovative strategies survive COVID-19 pandemic.

Language: Английский

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The Good and the Bad: Monocytes’ and Macrophages’ Diverse Functions in Inflammation

Cells, Journal Year: 2022, Volume and Issue: 11(12), P. 1979 - 1979

Published: June 20, 2022

Monocytes and macrophages are central players of the innate immune response play a pivotal role in regulation inflammation. Thereby, they actively participate all phases response, from initiating inflammation triggering adaptive through to clearance cell debris resolution In this review, we described mechanisms monocyte macrophage adaptation rapidly changing microenvironmental conditions discussed different forms polarization depending on environmental cues or pathophysiological condition. Therefore, special focus was placed tight pro- anti-inflammatory diverse functions S100A8/S100A9 proteins scavenger receptor CD163 were highlighted, respectively. We paid attention function under pathological conditions.

Language: Английский

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COVID-19 and cellular senescence

Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 23(4), P. 251 - 263

Published: Oct. 5, 2022

Language: Английский

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Monocyte-derived alveolar macrophages autonomously determine severe outcome of respiratory viral infection

Science Immunology, Journal Year: 2022, Volume and Issue: 7(73)

Published: July 1, 2022

Various lung insults can result in replacement of resident alveolar macrophages (AM) by bone marrow monocyte–derived (BMo)–AM. However, the dynamics this process and its long-term consequences for respiratory viral infections remain unclear. Using several mouse models a marker to unambiguously track fetal (FeMo)–AM BMo-AM, we established kinetics extent replenishment their function recurrent influenza A virus (IAV) infection. massive loss FeMo-AM resulted rapid self-renewal survivors, followed generation BMo-AM. BMo-AM progressively outcompeted over months, was due increased glycolytic proliferative capacity. The presence both naïve experienced conferred severe pathology IAV infection, which associated with proinflammatory phenotype. Furthermore, upon aging mice, were gradually replaced contributed disease severity cell-autonomous manner. Together, our results suggest that origin rather than training AM determines infection provide an explanation seen elderly.

Language: Английский

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Immune mechanisms underlying COVID-19 pathology and post-acute sequelae of SARS-CoV-2 infection (PASC)

eLife, Journal Year: 2023, Volume and Issue: 12

Published: May 26, 2023

With a global tally of more than 500 million cases severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections to date, there are growing concerns about the post-acute sequelae SARS-CoV-2 infection (PASC), also known as long COVID. Recent studies suggest that exaggerated immune responses key determinants severity and outcomes initial well subsequent PASC. The complexity innate adaptive in period requires in-depth mechanistic analyses identify specific molecular signals cell populations which promote PASC pathogenesis. In this review, we examine current literature on mechanisms dysregulation COVID-19 limited emerging data immunopathology While phases may share some parallel immunopathology, it is likely quite distinct heterogeneous, thus requiring large-scale longitudinal patients with without after an infection. By outlining knowledge gaps PASC, hope provide avenues for novel research directions will ultimately lead precision therapies restore healthy function patients.

Language: Английский

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Signaling pathways in macrophages: molecular mechanisms and therapeutic targets

MedComm, Journal Year: 2023, Volume and Issue: 4(5)

Published: Sept. 11, 2023

Abstract Macrophages play diverse roles in development, homeostasis, and immunity. Accordingly, the dysfunction of macrophages is involved occurrence progression various diseases, such as coronavirus disease 2019 atherosclerosis. The protective or pathogenic effect that exert different conditions largely depends on their functional plasticity, which regulated via signal transduction Janus kinase–signal transducer activator transcription, Wnt Notch pathways, stimulated by environmental cues. Over past few decades, molecular mechanisms signaling pathways have been gradually elucidated, providing more alternative therapeutic targets for diseases treatment. Here, we provide an overview basic physiology expound regulatory within them. We also address crucial role pathogenesis including autoimmune, neurodegenerative, metabolic, infectious cancer, with a focus advances macrophage‐targeted strategies exploring modulation components regulators pathways. Last, discuss challenges possible solutions therapy clinical applications. hope this comprehensive review will directions further research targeting macrophage are promising to improve efficacy

Language: Английский

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Pathogenesis of influenza and SARS-CoV-2 co-infection at the extremes of age: decipher the ominous tales of immune vulnerability

Advanced Biotechnology, Journal Year: 2025, Volume and Issue: 3(1)

Published: Jan. 21, 2025

The co-circulation of influenza and SARS-CoV-2 has led to co-infection events, primarily affecting children older adults, who are at higher risk for severe disease. Although prevalence is relatively low, it associated with worse outcomes compared mono-infections. Previous studies have shown that the depend on multiple factors, including viral interference, virus-host interaction host response. Children elderly exhibit distinct patterns antiviral response, which involve airway epithelium, mucociliary clearance, innate adaptive immune cells, inflammatory mediators. This review explores pathogeneses co-infection, focusing responses in elderly. By comparing immature immunity senescence we aim provide insights clinical management cases.

Language: Английский

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A randomized, placebo-controlled trial of the BTK inhibitor zanubrutinib in hospitalized patients with COVID-19 respiratory distress: immune biomarker and clinical findings

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 21, 2025

Background Cytokine release triggered by a hyperactive immune response is thought to contribute severe acute respiratory syndrome coronavirus 2019 (SARS-CoV-2)–related failure. Bruton tyrosine kinase (BTK) involved in innate immunity, and BTK inhibitors block cytokine release. We assessed the next-generation inhibitor zanubrutinib SARS-CoV-2–infected patients with distress. Method Cohort 1 had prospective, randomized, double-blind, placebo-controlled design; cohort 2 single-arm design. Adults SARS-CoV-2 requiring hospitalization (without mechanical ventilation) were randomized 1. Those on ventilation ≤24 hours enrolled 2. Patients 1:1 320 mg once daily or placebo (cohort 1), received 2). Co-primary endpoints failure-free survival rate time return breathing room air at 28 days. Corollary studies assess zanubrutinib’s impact performed. Results Sixty-three (n=30) (n=33), median treatment duration of 8.5 7.0 days, respectively. The (n=4) was 13 days; all discontinued early. In 1, estimated rates not returning day significantly different between treatments. Importantly, serological disease (COVID-19) impacted zanubrutinib. Lower levels granulocyte colony-stimulating factor, interleukin (IL)-10, monocyte chemoattractant protein-1, IL-4, IL-13 observed zanubrutinib-treated patients. Moreover, single-cell transcriptome analysis showed significant downregulation inflammatory mediators (IL-6, IL-8, macrophage protein-1α, IL-1β) signaling pathways (JAK1, STAT3, TYK2), activation gamma-delta T cells Conclusions Marked reduction preserved hospitalized COVID-19 distress receiving Despite these immunological findings, did show improvement over clinical recovery from Concurrent administration steroids antiviral therapy most may have contributed results. Investigation be warranted other settings where cell exhaustion are important. Clinical Trial Registration https://www.clinicaltrials.gov/study/NCT04382586 , identifier NCT04382586.

Language: Английский

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Liquid biomarkers of macrophage dysregulation and circulating spike protein illustrate the biological heterogeneity in patients with post‐acute sequelae of COVID‐19

Journal of Medical Virology, Journal Year: 2022, Volume and Issue: 95(1)

Published: Dec. 2, 2022

Post-acute sequelae of COVID-19 (PASC) are long-term consequences SARS-CoV-2 infection that can substantially impair the quality life. Underlying mechanisms ranging from persistent viruses to innate and adaptive immune dysregulation have been discussed. Here, we profiled plasma 181 individuals cohort study for digital health research in Germany (DigiHero), including after mild moderate with or without PASC uninfected controls. We focused on soluble factors related monocyte/macrophage biology circulating spike (S1) protein as a potential biomarker viral reservoirs. At median time 8 months infection, found pronounced almost all tested factors, both pro-inflammatory pro-fibrotic cytokines. These immunological perturbations were remarkably independent ongoing symptoms per se, but further correlation regression analyses suggested PASC-specific patterns involving CCL2/MCP-1 IL-8 either correlated sCD162, sCD206/MMR, IFN-α2, IL-17A IL-33, IL-18 IL-23. None analyzed detectability levels S1, indicating this represents an subset patients PASC. data confirm prior evidence persistence illustrate its biological heterogeneity still awaits clinically defined subtypes.

Language: Английский

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