Evidence map›Paper›PMID 34576716›Full record

ArticleMicroorganisms2021

TLR3 and TLR7 RNA Sensor Activation during SARS-CoV-2 Infection.

Daria Bortolotti, Valentina Gentili, Sabrina Rizzo, Giovanna Schiuma, Silvia Beltrami, Giovanni Strazzabosco, Mercedes Fernandez, Francesca Caccuri, Arnaldo Caruso, Roberta Rizzo

Open access · goldAbstract read
In one paragraph

Article in Microorganisms, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
136citing papers in PubMed, 4 pooled it
23.4field-weighted citation impact, top 1% 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

136 citing papers in PubMed, 4 syntheses or guidelines pooled it, 186 citations in OpenAlex.

  1. Mucosal immune response in biology, disease prevention and treatment.Signal transduction and targeted therapy · 2025
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  16. The Dual Role of Natural Killer Cells in the Septic Liver.Journal of inflammation research · 2026
    Review
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  19. Article
  20. Review

76 more citing papers are in PubMed but not listed here.

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 2 institutions in 1 country.

Daria BortolottiDepartment of Chemical, Pharmaceutical and Agricultural Science, University of Ferrara, 44121 Ferrara, Italy.ORCID 0000-0003-4496-9561
Valentina GentiliDepartment of Chemical, Pharmaceutical and Agricultural Science, University of Ferrara, 44121 Ferrara, Italy.ORCID 0000-0003-4572-5497
Sabrina RizzoDepartment of Chemical, Pharmaceutical and Agricultural Science, University of Ferrara, 44121 Ferrara, Italy.ORCID 0000-0002-9246-136X
Giovanna SchiumaDepartment of Chemical, Pharmaceutical and Agricultural Science, University of Ferrara, 44121 Ferrara, Italy.ORCID 0000-0003-4652-5550
Silvia BeltramiDepartment of Chemical, Pharmaceutical and Agricultural Science, University of Ferrara, 44121 Ferrara, Italy.ORCID 0000-0002-5923-9265
Giovanni StrazzaboscoDepartment of Chemical, Pharmaceutical and Agricultural Science, University of Ferrara, 44121 Ferrara, Italy.
Mercedes FernandezDepartment of Chemical, Pharmaceutical and Agricultural Science, University of Ferrara, 44121 Ferrara, Italy.ORCID 0000-0003-1237-5275
Francesca CaccuriDepartment of Microbiology and Virology, "Spedali Civili," 25126 Brescia, Italy.
Arnaldo CarusoDepartment of Microbiology and Virology, "Spedali Civili," 25126 Brescia, Italy.
Roberta RizzoDepartment of Chemical, Pharmaceutical and Agricultural Science, University of Ferrara, 44121 Ferrara, Italy.ORCID 0000-0001-9507-9126
University of Ferrara · ITAzienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia · IT

Funding

Università degli Studi di Ferrara Crowfounding 2021Università degli Studi di Ferrara FAR 2019; 2020
6 · The paper itself

Abstract

(1) Background: Acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent for the coronavirus disease (COVID-19) that has led to a pandemic that began in March 2020. The role of the SARS-CoV-2 components on innate and adaptive immunity is still unknown. We investigated the possible implication of pathogen-associated molecular patterns (PAMPs)-pattern recognition receptors (PRRs) interaction. (2) Methods: We infected Calu-3/MRC-5 multicellular spheroids (MTCSs) with a SARS-CoV-2 clinical strain and evaluated the activation of RNA sensors, transcription factors, and cytokines/interferons (IFN) secretion, by quantitative real-time PCR, immunofluorescence, and ELISA. (3) Results: Our results showed that the SARS-CoV-2 infection of Calu-3/MRC-5 multicellular spheroids induced the activation of the TLR3 and TLR7 RNA sensor pathways. In particular, TLR3 might act via IRF3, producing interleukin (IL)-1α, IL-1β, IL-4, IL-6, and IFN-α and IFN-β, during the first 24 h post-infection. Then, TLR3 activates the NFκB transduction pathway, leading to pro-inflammatory cytokine secretion. Conversely, TLR7 seems to mainly act via NFκB, inducing type 1 IFN, IFN-γ, and IFN-λ3, starting from the 48 h post-infection. (4) Conclusion: We showed that both TLR3 and TLR7 are involved in the control of innate immunity during lung SARS-CoV-2 infection. The activation of TLRs induced pro-inflammatory cytokines, such as IL-1α, IL-1β, IL-4, and IL-6, as well as interferons. TLRs could be a potential target in controlling the infection in the early stages of the disease.

Indexed as

RNA sensorsSARS-CoV-2TLR

Identifiers

PMID34576716
PMCPMC8465566
OpenAlexW3197807723

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.