@article {Saichi2020.07.20.212837, author = {Melissa Saichi and Maha Zohra Ladjemi and Sarantis Korniotis and Christophe Rousseau and Zakaria Ait-Hamou and Lucile Massenet and Elise Amblard and Floriane Noel and Yannick Marie and Delphine Bouteiller and Jasna Medvedovic and Fr{\'e}d{\'e}ric P{\`e}ne and Vassili Soumelis}, title = {Single cell RNA sequencing of blood antigen-presenting cells in severe Covid-19 reveals multi-process defects in antiviral immunity}, elocation-id = {2020.07.20.212837}, year = {2020}, doi = {10.1101/2020.07.20.212837}, publisher = {Cold Spring Harbor Laboratory}, abstract = {COVID-19 can lead to life-threatening acute respiratory failure, characterized by simultaneous increase in inflammatory mediators and viral load. The underlying cellular and molecular mechanisms remain unclear. We performed single-cell RNA-sequencing to establish an exhaustive high-resolution map of blood antigen-presenting cells (APC) in 7 COVID-19 patients with moderate or severe pneumonia, at day-1 and day-4 post-admission, and two healthy donors. We generated a unique dataset of 31,513 high quality APC, including monocytes and rare dendritic cell (DC) subsets. We uncovered multiprocess and previously unrecognized defects in anti-viral immune defense in specific APC compartments from severe patients: i) increase of pro-apoptotic genes exclusively in pDC, which are key effectors of antiviral immunity, ii) sharp decrease of innate sensing receptors, TLR7 and DHX9, in pDC and cDC1, respectively, iii) down-regulation of antiviral effector molecules, including Interferon stimulated genes (ISG) in all monocyte subsets, and iv) decrease of MHC class II-related genes, and MHC class II transactivator (CIITA) activity in cDC2, suggesting a viral inhibition of antigen presentation. These novel mechanisms may explain patient aggravation and suggest strategies to restore defective immune defense.Competing Interest StatementThe authors have declared no competing interest.}, URL = {https://www.biorxiv.org/content/early/2020/07/21/2020.07.20.212837}, eprint = {https://www.biorxiv.org/content/early/2020/07/21/2020.07.20.212837.full.pdf}, journal = {bioRxiv} }