Mary Wilson
Well-known member
Published: 08 February 2023
DOI https://doi.org/10.1038/s41467-023-36140-9
Manon Venet, Margarida Sa Ribeiro, Elodie Décembre, Alicia Bellomo, Garima Joshi, Célia Nuovo, Marine Villard, David Cluet, Magali Perret, Rémi Pescamona, Helena Paidassi, Thierry Walzer, Omran Allatif, Alexandre Belot, Sophie Trouillet-Assant, Emiliano P. Ricci & Marlène Dreux
Abstract
Type I and III interferons (IFN-I/λ) are important antiviral mediators against SARS-CoV-2 infection. Here, we demonstrate that plasmacytoid dendritic cells (pDC) are the predominant IFN-I/λ source following their sensing of SARS-CoV-2-infected cells. Mechanistically, this short-range sensing by pDCs requires sustained integrin-mediated cell adhesion with infected cells. In turn, pDCs restrict viral spread by an IFN-I/λ response directed toward SARS-CoV-2-infected cells. This specialized function enables pDCs to efficiently turn-off viral replication, likely via a local response at the contact site with infected cells. By exploring the pDC response in SARS-CoV-2 patients, we further demonstrate that pDC responsiveness inversely correlates with the severity of the disease. The pDC response is particularly impaired in severe COVID-19 patients. Overall, we propose that pDC activation is essential to control SARS-CoV-2-infection. Failure to develop this response could be important to understand severe cases of COVID-19.
https://www.nature.com/articles/s41467-023-36140-9#citeas
DOI https://doi.org/10.1038/s41467-023-36140-9
Manon Venet, Margarida Sa Ribeiro, Elodie Décembre, Alicia Bellomo, Garima Joshi, Célia Nuovo, Marine Villard, David Cluet, Magali Perret, Rémi Pescamona, Helena Paidassi, Thierry Walzer, Omran Allatif, Alexandre Belot, Sophie Trouillet-Assant, Emiliano P. Ricci & Marlène Dreux
Abstract
Type I and III interferons (IFN-I/λ) are important antiviral mediators against SARS-CoV-2 infection. Here, we demonstrate that plasmacytoid dendritic cells (pDC) are the predominant IFN-I/λ source following their sensing of SARS-CoV-2-infected cells. Mechanistically, this short-range sensing by pDCs requires sustained integrin-mediated cell adhesion with infected cells. In turn, pDCs restrict viral spread by an IFN-I/λ response directed toward SARS-CoV-2-infected cells. This specialized function enables pDCs to efficiently turn-off viral replication, likely via a local response at the contact site with infected cells. By exploring the pDC response in SARS-CoV-2 patients, we further demonstrate that pDC responsiveness inversely correlates with the severity of the disease. The pDC response is particularly impaired in severe COVID-19 patients. Overall, we propose that pDC activation is essential to control SARS-CoV-2-infection. Failure to develop this response could be important to understand severe cases of COVID-19.
https://www.nature.com/articles/s41467-023-36140-9#citeas