Evidence map›Paper›PMID 36713399›Full record

ArticleFrontiers in immunology2022

Distinct SARS-CoV-2 RNA fragments activate Toll-like receptors 7 and 8 and induce cytokine release from human macrophages and microglia.

Thomas Wallach, Martin Raden, Lukas Hinkelmann, Mariam Brehm, Dominik Rabsch, Hannah Weidling, Christina Krüger, Helmut Kettenmann, Rolf Backofen, Seija Lehnardt

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
5.8field-weighted citation impact, top 3% 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

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.

  1. Mucosal immune response in biology, disease prevention and treatment.Signal transduction and targeted therapy · 2025
    Pooled it
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  6. Review
  7. Article
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  13. miR-574-5p in epigenetic regulation and Toll-like receptor signaling.Cell communication and signaling : CCS · 2024
    Review
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  15. Article
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  18. Review
  19. Frontiers in immunology · 2024
    Article
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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

10 authors at 4 institutions in 1 country.

Thomas WallachInstitute of Cell Biology and Neurobiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Martin RadenBioinformatics, Department of Computer Science, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
Lukas HinkelmannInstitute of Cell Biology and Neurobiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Mariam BrehmInstitute of Cell Biology and Neurobiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Dominik RabschBioinformatics, Department of Computer Science, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
Hannah WeidlingInstitute of Cell Biology and Neurobiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Christina KrügerInstitute of Cell Biology and Neurobiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Helmut KettenmannCellular Neuroscience, Max Delbrueck Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
Rolf BackofenBioinformatics, Department of Computer Science, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
Seija LehnardtInstitute of Cell Biology and Neurobiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Humboldt-Universität zu Berlin · DEUniversity of Freiburg · DECharité - Universitätsmedizin Berlin · DEMax Delbrück Center · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: The pandemic coronavirus disease 19 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is marked by thromboembolic events and an inflammatory response throughout the body, including the brain. Methods: Employing the machine learning approach BrainDead we systematically screened for SARS-CoV-2 genome-derived single-stranded (ss) RNA fragments with high potential to activate the viral RNA-sensing innate immune receptors Toll-like receptor (TLR)7 and/or TLR8. Analyzing HEK TLR7/8 reporter cells we tested such RNA fragments with respect to their potential to induce activation of human TLR7 and TLR8 and to activate human macrophages, as well as iPSC-derived human microglia, the resident immune cells in the brain. Results: We experimentally validated several sequence-specific RNA fragment candidates out of the SARS-CoV-2 RNA fragments predicted in silico as activators of human TLR7 and TLR8. Moreover, these SARS-CoV-2 ssRNAs induced cytokine release from human macrophages and iPSC-derived human microglia in a sequence- and species-specific fashion. Discussion: Our findings determine TLR7 and TLR8 as key sensors of SARS-CoV-2-derived ssRNAs and may deepen our understanding of the mechanisms how this virus triggers, but also modulates an inflammatory response through innate immune signaling.

Indexed as

COVID-19CytokinesHumansMacrophagesMicrogliaRNA, ViralSARS-CoV-2Toll-Like Receptor 7Toll-Like Receptor 8CytokinesRNA, ViralToll-Like Receptor 7Toll-Like Receptor 8inflammatory responseiPSC-derived human microgliamacrophagesRNASARS-CoV-2toll-like receptors

Identifiers

PMID36713399
PMCPMC9880480
OpenAlexW4316040499

What OpenQuestion 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 OpenQuestion graph.