Nature communications · 2023
Severe COVID-19 patients have impaired plasmacytoid dendritic cell-mediated control of SARS-CoV-2.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Venet Manon, Ribeiro Margarida Sa, Décembre Elodie, Bellomo Alicia, Joshi Garima, Nuovo Célia, Villard Marine, Cluet David, Perret Magali, Pescamona Rémi, Paidassi Helena, Walzer Thierry, Allatif Omran, Belot Alexandre, Trouillet-Assant Sophie, Ricci Emiliano P, Dreux Marlène
Аннотация
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.