Severe COVID-19 patients have impaired plasmacytoid dendritic cell-mediated control of SARS-CoV-2

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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.

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Venet, M., Ribeiro, M. S., Décembre, E., Bellomo, A., Joshi, G., Nuovo, C., … Dreux, M. (2023). Severe COVID-19 patients have impaired plasmacytoid dendritic cell-mediated control of SARS-CoV-2. Nature Communications, 14(1). https://doi.org/10.1038/s41467-023-36140-9

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