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

(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 possi...

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Autores principales: Bortolotti, Daria, Gentili, Valentina, Rizzo, Sabrina, Schiuma, Giovanna, Beltrami, Silvia, Strazzabosco, Giovanni, Fernandez, Mercedes, Caccuri, Francesca, Caruso, Arnaldo, Rizzo, Roberta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465566/
https://www.ncbi.nlm.nih.gov/pubmed/34576716
http://dx.doi.org/10.3390/microorganisms9091820
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author Bortolotti, Daria
Gentili, Valentina
Rizzo, Sabrina
Schiuma, Giovanna
Beltrami, Silvia
Strazzabosco, Giovanni
Fernandez, Mercedes
Caccuri, Francesca
Caruso, Arnaldo
Rizzo, Roberta
author_facet Bortolotti, Daria
Gentili, Valentina
Rizzo, Sabrina
Schiuma, Giovanna
Beltrami, Silvia
Strazzabosco, Giovanni
Fernandez, Mercedes
Caccuri, Francesca
Caruso, Arnaldo
Rizzo, Roberta
author_sort Bortolotti, Daria
collection PubMed
description (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.
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spelling pubmed-84655662021-09-27 TLR3 and TLR7 RNA Sensor Activation during SARS-CoV-2 Infection Bortolotti, Daria Gentili, Valentina Rizzo, Sabrina Schiuma, Giovanna Beltrami, Silvia Strazzabosco, Giovanni Fernandez, Mercedes Caccuri, Francesca Caruso, Arnaldo Rizzo, Roberta Microorganisms Article (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. MDPI 2021-08-26 /pmc/articles/PMC8465566/ /pubmed/34576716 http://dx.doi.org/10.3390/microorganisms9091820 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bortolotti, Daria
Gentili, Valentina
Rizzo, Sabrina
Schiuma, Giovanna
Beltrami, Silvia
Strazzabosco, Giovanni
Fernandez, Mercedes
Caccuri, Francesca
Caruso, Arnaldo
Rizzo, Roberta
TLR3 and TLR7 RNA Sensor Activation during SARS-CoV-2 Infection
title TLR3 and TLR7 RNA Sensor Activation during SARS-CoV-2 Infection
title_full TLR3 and TLR7 RNA Sensor Activation during SARS-CoV-2 Infection
title_fullStr TLR3 and TLR7 RNA Sensor Activation during SARS-CoV-2 Infection
title_full_unstemmed TLR3 and TLR7 RNA Sensor Activation during SARS-CoV-2 Infection
title_short TLR3 and TLR7 RNA Sensor Activation during SARS-CoV-2 Infection
title_sort tlr3 and tlr7 rna sensor activation during sars-cov-2 infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465566/
https://www.ncbi.nlm.nih.gov/pubmed/34576716
http://dx.doi.org/10.3390/microorganisms9091820
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