TLR10 overexpression modulates immune response in A549 lung epithelial cells challenged with SARS-CoV-2 S and N proteins
Špela Knez, Mojca Narat, Jernej Ogorevc
Frontiers in Immunology, doi:10.3389/fimmu.2024.1490478
Toll-like receptors (TLRs) play an important role in the recognition of viral particles and activation of the innate immune system, but their role in SARS-CoV-2 infection is still poorly characterized. In the present study, we investigated the role of Toll-like receptor 10 (TLR10) in modulating the immune response during SARS-CoV-2 infection. The results showed that overexpression of TLR10 in A549 lung epithelial cells, immunostimulated with SARS-CoV-2 proteins S and N mainly downregulated proinflammatory cytokines and interferons and affected gene expression in the cocultured THP-1 monocytes. Our results suggest that TLR10 could mediate the extent of SARS-CoV-2 infection by downregulating the release of inflammatory cytokines and chemokines such as CXCL10, IL6, IL8, and IFNb. Modulation of TLR10 expression could have implications for the treatment of patients with severe COVID-19, in whom excessive inflammation leading to the development of acute respiratory distress syndrome (ARDS) is a key feature. However, further research is needed to fully understand the impact of modulating TLR10 expression on the antiviral response and the overall balance of the immune response during SARS-CoV-2 infection.
Ethics statement Ethical approval was not required for the studies on humans in accordance with the local legislation and institutional requirements because only commercially available established cell lines were used. Ethical approval was not required for the
Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Supplementary material The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fimmu.2024.1490478/ full#supplementary-material
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"abstract": "<jats:p>Toll-like receptors (TLRs) play an important role in the recognition of viral particles and activation of the innate immune system, but their role in SARS-CoV-2 infection is still poorly characterized. In the present study, we investigated the role of Toll-like receptor 10 (TLR10) in modulating the immune response during SARS-CoV-2 infection. The results showed that overexpression of <jats:italic>TLR10</jats:italic> in A549 lung epithelial cells, immunostimulated with SARS-CoV-2 proteins S and N mainly downregulated proinflammatory cytokines and interferons and affected gene expression in the cocultured THP-1 monocytes. Our results suggest that TLR10 could mediate the extent of SARS-CoV-2 infection by downregulating the release of inflammatory cytokines and chemokines such as <jats:italic>CXCL10</jats:italic>, <jats:italic>IL6</jats:italic>, <jats:italic>IL8</jats:italic>, and <jats:italic>IFNβ</jats:italic>. Modulation of <jats:italic>TLR10</jats:italic> expression could have implications for the treatment of patients with severe COVID-19, in whom excessive inflammation leading to the development of acute respiratory distress syndrome (ARDS) is a key feature. However, further research is needed to fully understand the impact of modulating <jats:italic>TLR10</jats:italic> expression on the antiviral response and the overall balance of the immune response during SARS-CoV-2 infection.</jats:p>",
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