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

Plasmacytoid DC (pDC) have been shown to secrete type I IFN and to be involved in controlling replication and spread of some viruses. Here the authors show that in severe SARS-CoV-2 infection pDC function is impaired leading to reduced type I IFN production and possibly lower viral control. Type I and III interferons (IFN-I/lambda) are important antiviral mediators against SARS-CoV-2 infection. Here, we demonstrate that plasmacytoid dendritic cells (pDC) are the predominant IFN-I/lambda 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/lambda 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.

Automated summary

The authors demonstrate that in severe SARS-CoV-2 infection, the function of plasmacytoid dendritic cells (pDC) is impaired, leading to reduced production of type I interferon and possibly lower viral control. This study suggests that pDC activation is essential to control SARS-CoV-2 infection, and failure to develop this response could be important in understanding severe cases of COVID-19.