SARS-CoV-2 induces human plasmacytoid predendritic cell diversification via UNC93B and IRAK4
| Autor: | Emmanuelle Jouanguy, Jean-Michel Molina, Jean-Laurent Casanova, Jérôme Le Goff, Constance Delaugerre, Lucie Bonnet-Madin, Laurent Meertens, Capucine Picard, Ali Amara, Shen-Ying Zhang, Vassili Soumelis, Fanny Onodi, Qian Zhang, Léa Karpf, Justine Poirot, Anne Puel |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
UNC93B1 viruses Cell Plasticity Innate Immunity and Inflammation Immunology C-C chemokine receptor type 7 macromolecular substances Biology Article Immunophenotyping Immunomodulation Interferon Lambda Infectious Disease and Host Defense 03 medical and health sciences 0302 clinical medicine Immune system Immunity Humans Immunology and Allergy CD86 Effector SARS-CoV-2 Brief Definitive Report virus diseases COVID-19 Membrane Transport Proteins hemic and immune systems Dendritic cell Dendritic Cells biochemical phenomena metabolism and nutrition IRAK4 3. Good health COVID-19 Drug Treatment 030104 developmental biology Interleukin-1 Receptor-Associated Kinases Host-Pathogen Interactions Interferon Type I Cytokines Interferons Inflammation Mediators CD80 Biomarkers 030215 immunology Hydroxychloroquine |
| Zdroj: | Journal of Experimental Medicine The Journal of Experimental Medicine bioRxiv article-version (status) pre article-version (number) 2 |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.20201387 |
| Popis: | Plasmacytoid dendritic cells (pDCs) are not permissive to SARS-CoV-2 infection but, upon viral exposure, differentiate into subsets and rapidly produce type I and III interferons. Mechanistically, pDC activation depends on IRAK4 and UNC93B1 expression. 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. Graphical Abstract |
| Databáze: | OpenAIRE |
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