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

The Journal of experimental medicine 2021 Apr 05

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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. © 2021 Onodi et al.

Citation

Fanny Onodi, Lucie Bonnet-Madin, Laurent Meertens, Léa Karpf, Justine Poirot, Shen-Ying Zhang, Capucine Picard, Anne Puel, Emmanuelle Jouanguy, Qian Zhang, Jérôme Le Goff, Jean-Michel Molina, Constance Delaugerre, Jean-Laurent Casanova, Ali Amara, Vassili Soumelis. SARS-CoV-2 induces human plasmacytoid predendritic cell diversification via UNC93B and IRAK4. The Journal of experimental medicine. 2021 Apr 05;218(4)