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bioRxiv · 10.1101/2020.07.10.197343

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

Fanny Onodi·Lucie Bonnet-Madin·Léa Karpf·Laurent Meertens·Justine Poirot·Jerôme LeGoff·Constance Delaugerre·Ali AMARA·Vassili Soumelis
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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-, interferon-{lambda}1, 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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Fanny Onodi, Lucie Bonnet-Madin, Léa Karpf, Laurent Meertens, Justine Poirot, Jerôme LeGoff, Constance Delaugerre, Ali AMARA, Vassili Soumelis. 2020-07-10. SARS-CoV-2 induces activation and diversification of human plasmacytoid pre-dendritic cells.. https://doi.org/10.1101/2020.07.10.197343

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