Single-cell RNA sequencing of blood antigen-presenting cells in severe COVID-19 reveals multi-process defects in antiviral immunity.
Nat Cell Biol
; 23(5): 538-551, 2021 05.
Article
in English
| MEDLINE | ID: covidwho-1223094
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Antigen Presentation
/
COVID-19
/
Antigens, Viral
Limits:
Humans
Language:
English
Journal:
Nat Cell Biol
Year:
2021
Document Type:
Article
Affiliation country:
S41556-021-00681-2
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