ArticleCell communication and signaling : CCS2023
SARS-CoV-2 primed platelets-derived microRNAs enhance NETs formation by extracellular vesicle transmission and TLR7/8 activation.
Article in Cell communication and signaling : CCS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Let-7a-5p/SHIP-1 Axis Drives SARS-CoV-2 Spike-1-Induced Microglial Pyroptosis.International journal of molecular sciences · 2026Article
- Investigating the Role of microRNA in Host-Influenza A and Other Respiratory RNA Virus Interactions.Pathogens (Basel, Switzerland) · 2026Review
- Mast cells release DNA Extracellular Traps (DETs) in response to SARS-CoV-2 and its spike protein.Cell communication and signaling : CCS · 2026Article
- Viral Comorbidities Remodel Host Transcriptome and Redox Signaling in an NADPH Oxidase Isoform-Specific Manner.Viruses · 2026Review
- Extracellular Vesicle-Delivered tRF-His-GTG-1 Reprograms Neutrophil Lipophagy and Triggers Inflammation in COVID-19.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- MicroRNAs in Acute COVID-19 and Long COVID: Dysregulation, Pathogenic Roles, and Clinical Implications.Journal of immunology research · 2026Review
- miRNAs-neutrophil axis: novel insights into acute lung injury and chronic inflammatory lung diseases.Frontiers in immunology · 2026Review
- Toll-like Receptor 7 Deficiency Attenuates Platelet Dysfunction in Sepsis.Biomolecules · 2025Article
- Extracellular vesicles in metabolic perspective: mechanism and targeted therapy.Journal of nanobiotechnology · 2025Review
- Activation of toll‑like receptors by non‑coding RNAs and their fragments (Review).Molecular medicine reports · 2025Review
- Diversity of extracellular vesicle sources in atherosclerosis: role and therapeutic application.Angiogenesis · 2025Review
- Cytosolic nucleic acid sensing as driver of critical illness: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2025Review
- Dual Role of Extracellular Vesicles as Orchestrators of Emerging and Reemerging Virus Infections.Cell biochemistry and biophysics · 2025Review
- Neutrophil extracellular traps: a catalyst for atherosclerosis.Molecular and cellular biochemistry · 2024Review
- miR-574-5p in epigenetic regulation and Toll-like receptor signaling.Cell communication and signaling : CCS · 2024Review
- Extracellular Vesicle microRNA: A Promising Biomarker and Therapeutic Target for Respiratory Diseases.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHyperactive neutrophil extracellular traps (NETs) formation plays a key role in the pathogenesis of severe COVID-19. Extracellular vesicles (EVs) are vehicles which carry cellular components for intercellular communication. The association between COVID-19 patients-derived EVs and NETs formation remains elusive.
methodsWe explored the roles of EVs in NETs formation from 40 COVID-19 patients with different disease severities as well as 30 healthy subjects. The EVs-carried microRNAs profile was analyzed using next generation sequencing approach which was validated by quantitative reverse transcription PCR. The regulatory mechanism of EVs on NETs formation was investigated by using an in vitro cell-based assay, including immunofluorescence assay, flow cytometry, and immunoblotting.
resultsCOVID-19 patient-derived EVs induced NETs formation by endocytosis uptake. SARS-CoV-2 spike protein-triggered NETs formation was significantly enhanced in the presence of platelet-derived EVs (pEVs) and this effect was Toll-like receptor (TLR) 7/8- and NADPH oxidase-dependent. Increased levels of miR-21/let-7b were revealed in EVs from COVID-19 patients and were associated with disease severity. We demonstrated that the spike protein activated platelets directly, followed by the subsequent intracellular miR-21/let-7b upregulation and then were loaded into pEVs. The pEVs-carried miR-21 interacted with TLR7/8 to prime p47phox phosphorylation in neutrophils, resulting in NADPH oxidase activation to promote ROS production and NETs enhancement. In addition, miR-21 modulates NF-κB activation and IL-1β/TNFα/IL-8 upregulation in neutrophils upon TLR7/8 engagement. The miR-21 inhibitor and TLR8 antagonist could suppress efficiently spike protein-induced NETs formation and pEVs primed NETs enhancement.
conclusionsWe identified SARS-CoV-2 triggered platelets-derived GU-enriched miRNAs (e.g., miR-21/let-7b) as a TLR7/8 ligand that could activate neutrophils through EVs transmission. The miR-21-TLR8 axis could be used as a potential predisposing factor or therapeutic target for severe COVID-19.
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