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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8465566 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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