SARS-CoV-2 induces human plasmacytoid predendritic cell diversification via UNC93B and IRAK4.
J Exp Med
; 218(4)2021 04 05.
Article
in English
| MEDLINE | ID: covidwho-1061104
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 predendritic cells (pDCs), a key player in antiviral immunity. We show that pDCs 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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Membrane Transport Proteins
/
Dendritic Cells
/
Interleukin-1 Receptor-Associated Kinases
/
Cell Plasticity
/
SARS-CoV-2
/
COVID-19
Type of study:
Prognostic study
Topics:
Long Covid
Limits:
Humans
Language:
English
Year:
2021
Document Type:
Article
Affiliation country:
Jem.20201387
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