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Severe COVID-19 patients have impaired plasmacytoid dendritic cell-mediated control of SARS-CoV-2.
Nat Commun, 14(1):694.
Type I and III interferons (IFN-I/λ) are important antiviral mediators againstSARS-CoV-2 infection. Here, we demonstrate that plasmacytoid dendritic cells(pDC) are the predominant IFN-I/λ source following their sensing ofSARS-CoV-2-infected cells. Mechanistically, this short-range sensing by pDCsrequires sustained integrin-mediated cell adhesion with infected cells. In turn,pDCs restrict viral spread by an IFN-I/λ response directed towardSARS-CoV-2-infected cells. This specialized function enables pDCs to efficientlyturn-off viral replication, likely via a local response at the contact site withinfected cells. By exploring the pDC response in SARS-CoV-2 patients, we furtherdemonstrate that pDC responsiveness inversely correlates with the severity of thedisease. The pDC response is particularly impaired in severe COVID-19 patients.Overall, we propose that pDC activation is essential to controlSARS-CoV-2-infection. Failure to develop this response could be important tounderstand severe cases of COVID-19.
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