SARS-CoV-2 induces activation and diversification of human plasmacytoid pre-dendritic cells.

BioRxiv : the Preprint Server for Biology
Fanny OnodiVassili Soumelis

Abstract

Several studies have analyzed antiviral immune pathways in severe COVID-19 patients. However, the initial steps of antiviral immunity are not known. Here, we have studied the interaction of isolated primary SARS-CoV-2 viral strains with human plasmacytoid pre-dendritic cells (pDC), a key player in antiviral immunity. We show that pDC are not permissive to SARS-CoV-2 infection. However, they efficiently diversified into activated P1-, P2-, and P3-pDC effector subsets in response to viral stimulation. They expressed checkpoint molecules 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. Importantly, all major aspects of SARS-CoV-2-induced pDC activation were inhibited by hydroxychloroquine, including P2- and P3-pDC differentiation, the expression of maturation markers, and the production of interferon-α and inflammatory cytokines. Our results indicate that pDC may represent a major player in the first line of defense against SARS-CoV-2 infection, and call for caution in the use of hydroxychloroquine in the early treatment of the disease.Competing Interest StatementThe authors have declared no competing interest.

Methods Mentioned

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

Related Concepts

Related Feeds

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

Antimalarial Agents (ASM)

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.

Antimalarial Agents

Antimalarial agents, also known as antimalarials, are designed to prevent or cure malaria. Discover the latest research on antimalarial agents here.