Evidence map›Paper›PMID 36497044›Full record

ArticleCells2022

SARS-CoV-2-Associated ssRNAs Activate Human Neutrophils in a TLR8-Dependent Fashion.

Elisa Gardiman, Francisco Bianchetto-Aguilera, Sara Gasperini, Laura Tiberio, Matteo Scandola, Virginia Lotti, Davide Gibellini, Valentina Salvi, Daniela Bosisio, Marco A Cassatella and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.0field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Article
  3. Cytosolic proliferating cell nuclear antigen (PCNA) orchestrates neutrophil hyperactivation in COVID-19.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  4. SARS-CoV-2 uptake and inflammatory response in senescent endothelial cells are regulated by the BSG/VEGFR2 pathway.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. miR-574-5p in epigenetic regulation and Toll-like receptor signaling.Cell communication and signaling : CCS · 2024
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Elisa GardimanGeneral Pathology Section, Department of Medicine, University of Verona, 37134 Verona, Italy.ORCID 0000-0002-5431-9610
Francisco Bianchetto-AguileraGeneral Pathology Section, Department of Medicine, University of Verona, 37134 Verona, Italy.ORCID 0000-0003-3910-4715
Sara GasperiniGeneral Pathology Section, Department of Medicine, University of Verona, 37134 Verona, Italy.
Laura TiberioDepartment of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.ORCID 0000-0003-0482-9898
Matteo ScandolaGeneral Pathology Section, Department of Medicine, University of Verona, 37134 Verona, Italy.
Virginia LottiMicrobiology Section, Department of Diagnostic and Public Health, University of Verona, 37134 Verona, Italy.ORCID 0000-0002-5746-3810
Davide GibelliniMicrobiology Section, Department of Diagnostic and Public Health, University of Verona, 37134 Verona, Italy.
Valentina SalviDepartment of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
Daniela BosisioDepartment of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.ORCID 0000-0001-6276-5365
Marco A CassatellaGeneral Pathology Section, Department of Medicine, University of Verona, 37134 Verona, Italy.
Nicola TamassiaGeneral Pathology Section, Department of Medicine, University of Verona, 37134 Verona, Italy.ORCID 0000-0003-2990-3003
University of Verona · ITUniversity of Brescia · IT

Funding

Fondazione Cariverona Bando Ricerca Scientifica 2017Italian Association for Cancer Research IG-20339Ministero della Salute GR-2016-02361263Ministry of Education, Universities and Research 20177J4E75_004
6 · The paper itself

Abstract

COVID-19 disease is characterized by a dysregulation of the innate arm of the immune system. However, the mechanisms whereby innate immune cells, including neutrophils, become activated in patients are not completely understood. Recently, we showed that GU-rich RNA sequences from the SARS-CoV-2 genome (i.e., SCV2-RNA1 and SCV2-RNA2) activate dendritic cells. To clarify whether human neutrophils may also represent targets of SCV2-RNAs, neutrophils were treated with either SCV2-RNAs or, as a control, R848 (a TLR7/8 ligand), and were then analyzed for several functional assays and also subjected to RNA-seq experiments. Results highlight a remarkable response of neutrophils to SCV2-RNAs in terms of TNFα, IL-1ra, CXCL8 production, apoptosis delay, modulation of CD11b and CD62L expression, and release of neutrophil extracellular traps. By RNA-seq experiments, we observed that SCV2-RNA2 promotes a transcriptional reprogramming of neutrophils, characterized by the induction of thousands of proinflammatory genes, similar to that promoted by R848. Furthermore, by using CU-CPT9a, a TLR8-specific inhibitor, we found that SCV2-RNA2 stimulates neutrophils exclusively via TLR8-dependent pathways. In sum, our study proves that single-strand RNAs from the SARS-CoV-2 genome potently activate human neutrophils via TLR8, thus uncovering a potential mechanism whereby neutrophils may contribute to the pathogenesis of severe COVID-19 disease.

Indexed as

NeutrophilsRNA, ViralSARS-CoV-2Toll-Like Receptor 8COVID-19HumansRNA, ViralTLR8 protein, humanToll-Like Receptor 8COVID-19neutrophil extracellular trapneutrophilsRNA-seqSARS-CoV-2ssRNATLR8

Identifiers

PMID36497044
PMCPMC9738506
OpenAlexW4310211240

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.