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Citation
Tags
HERO ID
7300730
Reference Type
Journal Article
Title
SARS-CoV-2 induces human plasmacytoid pre-dendritic cell diversification via UNC93B and IRAK4
Author(s)
Onodi, F; Bonnet-Madin, L; Meertens, L; Karpf, L; Poirot, J; Zhang, SY; Picard, C; Puel, A; Jouanguy, E; Zhang, Q; Le Goff, J; Molina, JM; Delaugerre, C; Casanova, JL; Amara, A; Soumelis, V
Year
2021
Is Peer Reviewed?
Yes
Journal
Journal of Experimental Medicine
ISSN:
0022-1007
EISSN:
1540-9538
Volume
218
Issue
4
Language
English
PMID
33442685
DOI
10.1101/2020.07.10.197343
Web of Science Id
WOS:000630061100001
Abstract
Several studies have analyzed antiviral immune pathways in late-stage severe COVID-19. However, the initial steps of SARS-CoV-2 antiviral immunity are poorly understood. Here, we have isolated primary SARS-CoV-2 viral strains, and studied their interaction with human plasmacytoid pre-dendritic cells (pDC), a key player in antiviral immunity. We show that pDC are not productively infected by SARS-CoV-2. However, they efficiently diversified into activated P1-, P2-, and P3-pDC effector subsets in response to viral stimulation. They expressed CD80, CD86, CCR7, and OX40 ligand at levels similar to influenza virus-induced activation. They rapidly produced high levels of interferon-α, interferon-λ1, IL-6, IP-10, and IL-8. All major aspects of SARS-CoV-2-induced pDC activation were inhibited by hydroxychloroquine. Mechanistically, SARS-CoV-2-induced pDC activation critically depended on IRAK4 and UNC93B1, as established using pDC from genetically deficient patients. Overall, our data indicate that human pDC are efficiently activated by SARS-CoV-2 particles and may thus contribute to type I IFN-dependent immunity against SARS-CoV-2 infection.
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