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

Department of Chemical, Pharmaceutical and Agricultural Science, University of Ferrara, 44121 Ferrara, Italy
Department of Microbiology and Virology, “Spedali Civili,” 25126 Brescia, Italy
LTTA, University of Ferrara, 44121 Ferrara, Italy
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Andrea Marzi
Microorganisms 2021, 9(9), 1820;
Received: 23 July 2021 / Revised: 22 August 2021 / Accepted: 23 August 2021 / Published: 26 August 2021
(This article belongs to the Special Issue SARS-CoV-2 Systemic Effects: New Clues)
(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. View Full-Text
Keywords: SARS-CoV-2; TLR; RNA sensors SARS-CoV-2; TLR; RNA sensors
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MDPI and ACS Style

Bortolotti, D.; Gentili, V.; Rizzo, S.; Schiuma, G.; Beltrami, S.; Strazzabosco, G.; Fernandez, M.; Caccuri, F.; Caruso, A.; Rizzo, R. TLR3 and TLR7 RNA Sensor Activation during SARS-CoV-2 Infection. Microorganisms 2021, 9, 1820.

AMA Style

Bortolotti D, Gentili V, Rizzo S, Schiuma G, Beltrami S, Strazzabosco G, Fernandez M, Caccuri F, Caruso A, Rizzo R. TLR3 and TLR7 RNA Sensor Activation during SARS-CoV-2 Infection. Microorganisms. 2021; 9(9):1820.

Chicago/Turabian Style

Bortolotti, Daria, Valentina Gentili, Sabrina Rizzo, Giovanna Schiuma, Silvia Beltrami, Giovanni Strazzabosco, Mercedes Fernandez, Francesca Caccuri, Arnaldo Caruso, and Roberta Rizzo. 2021. "TLR3 and TLR7 RNA Sensor Activation during SARS-CoV-2 Infection" Microorganisms 9, no. 9: 1820.

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