Severe COVID-19 patients have impaired plasmacytoid dendritic cell-mediated control of SARS-CoV-2.
Manon VenetMargarida Sa RibeiroElodie DécembreAlicia BellomoGarima JoshiCélia NuovoMarine VillardDavid CluetMagali PerretRémi PescamonaHelena PaidassiThierry WalzerOmran AlatiffAlexandre BelotSophie Trouillet-AssantEmiliano P RicciMarlène DreuxPublished in: Nature communications (2023)
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.
Keyphrases
- sars cov
- dendritic cells
- respiratory syndrome coronavirus
- induced apoptosis
- immune response
- regulatory t cells
- cell cycle arrest
- cell adhesion
- coronavirus disease
- ejection fraction
- endoplasmic reticulum stress
- end stage renal disease
- cell death
- fluorescent probe
- newly diagnosed
- oxidative stress
- pi k akt
- quantum dots
- drug induced
- peritoneal dialysis