학술논문
Single-cell RNA sequencing of blood antigen-presenting cells in severe COVID-19 reveals multi-process defects in antiviral immunity
Document Type
Report
Author
Source
Nature Cell Biology. May 2021, Vol. 23 Issue 5, p538, 14 p.
Subject
Language
English
ISSN
1465-7392
Abstract
Author(s): Melissa Saichi [sup.1] , Maha Zohra Ladjemi [sup.2] [sup.3] , Sarantis Korniotis [sup.1] , Christophe Rousseau [sup.2] , Zakaria Ait Hamou [sup.2] [sup.3] , Lucile Massenet-Regad [sup.1] [sup.4] , [...]
COVID-19 can lead to life-threatening respiratory failure, with increased inflammatory mediators and viral load. Here, we perform single-cell RNA-sequencing to establish a high-resolution map of blood antigen-presenting cells (APCs) in 15 patients with moderate or severe COVID-19 pneumonia, at day 1 and day 4 post admission to intensive care unit or pulmonology department, as well as in 4 healthy donors. We generated a unique dataset of 81,643 APCs, including monocytes and rare dendritic cell (DC) subsets. We uncovered multi-process defects in antiviral immune defence in specific APCs from patients with severe disease: (1) increased pro-apoptotic pathways in plasmacytoid DCs (pDCs, key effectors of antiviral immunity), (2) a decrease of the innate sensors TLR9 and DHX36 in pDCs and CLEC9a.sup.+ DCs, respectively, (3) downregulation of antiviral interferon-stimulated genes in monocyte subsets and (4) a decrease of major histocompatibility complex (MHC) class II-related genes and MHC class II transactivator activity in cDC1c.sup.+ DCs, suggesting viral inhibition of antigen presentation. These novel mechanisms may explain patient aggravation and suggest strategies to restore the defective immune defence. Saichi et al. performed single-cell RNA-seq analysis of antigen-presenting cells (APCs) isolated from the peripheral blood of patients with moderate and severe COVID-19 and uncovered defects in antiviral immune response in specific APC subsets.
COVID-19 can lead to life-threatening respiratory failure, with increased inflammatory mediators and viral load. Here, we perform single-cell RNA-sequencing to establish a high-resolution map of blood antigen-presenting cells (APCs) in 15 patients with moderate or severe COVID-19 pneumonia, at day 1 and day 4 post admission to intensive care unit or pulmonology department, as well as in 4 healthy donors. We generated a unique dataset of 81,643 APCs, including monocytes and rare dendritic cell (DC) subsets. We uncovered multi-process defects in antiviral immune defence in specific APCs from patients with severe disease: (1) increased pro-apoptotic pathways in plasmacytoid DCs (pDCs, key effectors of antiviral immunity), (2) a decrease of the innate sensors TLR9 and DHX36 in pDCs and CLEC9a.sup.+ DCs, respectively, (3) downregulation of antiviral interferon-stimulated genes in monocyte subsets and (4) a decrease of major histocompatibility complex (MHC) class II-related genes and MHC class II transactivator activity in cDC1c.sup.+ DCs, suggesting viral inhibition of antigen presentation. These novel mechanisms may explain patient aggravation and suggest strategies to restore the defective immune defence. Saichi et al. performed single-cell RNA-seq analysis of antigen-presenting cells (APCs) isolated from the peripheral blood of patients with moderate and severe COVID-19 and uncovered defects in antiviral immune response in specific APC subsets.