SARS-CoV-2 induces human plasmacytoid pre-dendritic cell diversification via UNC93B and IRAK4.

BioRxiv : the Preprint Server for Biology
Fanny OnodiVassili Soumelis

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.

Citations

Jan 28, 2021·International Journal of Molecular Sciences·Laura Kate GadanecVasso Apostolopoulos
May 1, 2021·International Journal of Molecular Sciences·Dóra BenczeKitti Pázmándi

Methods Mentioned

BETA
density gradient centrifugation
light microscopy
flow cytometry
PCR
enzyme-linked immunosorbent assay

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