Single-cell RNA sequencing of blood antigen-presenting cells in severe COVID-19 reveals multi-process defects in antiviral immunity
Single-cell RNA sequencing of blood antigen-presenting cells in severe COVID-19 reveals multi-process defects in antiviral immunity
复制标题
重症COVID-19患者血液抗原呈递细胞单细胞RNA测序揭示抗病毒免疫多过程缺陷
DOI：
10.1038/s41556-021-00681-2
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发表时间：
2021-05-10
影响因子：
21.3
通讯作者：
Soumelis, Vassili
中科院分区：
文献类型：
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作者：
Saichi, Melissa;Ladjemi, Maha Zohra;Soumelis, Vassili
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(+) 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(+) DCs, suggesting viral inhibition of antigen presentation. These novel mechanisms may explain patient aggravation and suggest strategies to restore the defective immune defence.
