SARS-CoV-2 induces human plasmacytoid pre-dendritic cell diversification via UNC93B and IRAK4.
Identifieur interne : 000173 ( Main/Exploration ); précédent : 000172; suivant : 000174SARS-CoV-2 induces human plasmacytoid pre-dendritic cell diversification via UNC93B and IRAK4.
Auteurs : Fanny Onodi [France] ; Lucie Bonnet-Madin [France] ; Laurent Meertens [France] ; Léa Karpf [France] ; Justine Poirot [France] ; Shen-Ying Zhang [États-Unis] ; Capucine Picard ; Anne Puel [États-Unis] ; Emmanuelle Jouanguy [États-Unis] ; Qian Zhang [États-Unis] ; Jérôme Le Goff [France] ; Jean-Michel Molina [France] ; Constance Delaugerre [France] ; Jean-Laurent Casanova [États-Unis] ; Ali Amara [France] ; Vassili Soumelis [France]Source :
- bioRxiv : the preprint server for biology ; 2021.
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.
DOI: 10.1101/2020.07.10.197343
PubMed: 33442685
PubMed Central: PMC7805442
Affiliations:
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Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Picard, Capucine" sort="Picard, Capucine" uniqKey="Picard C" first="Capucine" last="Picard">Capucine Picard</name><affiliation><nlm:affiliation>Université de Paris; INSERM UMR 1163 Institut Imagine, France EU.</nlm:affiliation><wicri:noCountry code="subField">France EU</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Study center for primary immunodeficiencies, Necker Hospital for Sick Children Assistance Publique-Hôpitaux (AP-HP) de Paris, Paris, France, EU.</nlm:affiliation><wicri:noCountry code="subField">EU</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Pediatric Hematology and Immunology Unit, Necker Hospital for Sick Children, AP-HP, Paris, France, EU.</nlm:affiliation><wicri:noCountry code="subField">EU</wicri:noCountry></affiliation></author><author><name sortKey="Puel, Anne" sort="Puel, Anne" uniqKey="Puel A" first="Anne" last="Puel">Anne Puel</name><affiliation><nlm:affiliation>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France, EU.</nlm:affiliation><wicri:noCountry code="subField">EU</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Université de Paris; INSERM UMR 1163 Institut Imagine, France EU.</nlm:affiliation><wicri:noCountry code="subField">France EU</wicri:noCountry></affiliation><affiliation wicri:level="2"><nlm:affiliation>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, 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York</region></placeName></affiliation></author><author><name sortKey="Le Goff, Jerome" sort="Le Goff, Jerome" uniqKey="Le Goff J" first="Jérôme" last="Le Goff">Jérôme Le Goff</name><affiliation wicri:level="3"><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, INSERM U976, Hôpital Saint-Louis, 75010 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Paris, Institut de Recherche Saint-Louis, INSERM U976, Hôpital Saint-Louis, 75010 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Laboratoire de Virologie et Département des Maladies Infectieuses, Hôpital Saint-Louis, APHP, 75010 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Virologie et Département des Maladies Infectieuses, Hôpital Saint-Louis, APHP, 75010 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Molina, Jean Michel" sort="Molina, Jean Michel" uniqKey="Molina J" first="Jean-Michel" last="Molina">Jean-Michel Molina</name><affiliation wicri:level="3"><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, INSERM U944 CNRS 7212, Hôpital Saint-Louis, 75010 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Paris, Institut de Recherche Saint-Louis, INSERM U944 CNRS 7212, Hôpital Saint-Louis, 75010 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Laboratoire de Virologie et Département des Maladies Infectieuses, Hôpital Saint-Louis, APHP, 75010 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Virologie et Département des Maladies Infectieuses, Hôpital Saint-Louis, APHP, 75010 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Delaugerre, Constance" sort="Delaugerre, Constance" uniqKey="Delaugerre C" first="Constance" last="Delaugerre">Constance Delaugerre</name><affiliation wicri:level="3"><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, INSERM U944 CNRS 7212, Hôpital Saint-Louis, 75010 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Paris, Institut de Recherche Saint-Louis, INSERM U944 CNRS 7212, Hôpital Saint-Louis, 75010 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Laboratoire de Virologie et Département des Maladies Infectieuses, Hôpital Saint-Louis, APHP, 75010 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Virologie et Département des Maladies Infectieuses, Hôpital Saint-Louis, APHP, 75010 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Casanova, Jean Laurent" sort="Casanova, Jean Laurent" uniqKey="Casanova J" first="Jean-Laurent" last="Casanova">Jean-Laurent Casanova</name><affiliation><nlm:affiliation>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France, EU.</nlm:affiliation><wicri:noCountry code="subField">EU</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Université de Paris; INSERM UMR 1163 Institut Imagine, France EU.</nlm:affiliation><wicri:noCountry code="subField">France EU</wicri:noCountry></affiliation><affiliation wicri:level="2"><nlm:affiliation>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation><nlm:affiliation>Pediatric Hematology and Immunology Unit, Necker Hospital for Sick Children, AP-HP, Paris, France, EU.</nlm:affiliation><wicri:noCountry code="subField">EU</wicri:noCountry></affiliation><affiliation wicri:level="2"><nlm:affiliation>Howard Hughes Medical Institute, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Howard Hughes Medical Institute, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Amara, Ali" sort="Amara, Ali" uniqKey="Amara A" first="Ali" last="Amara">Ali Amara</name><affiliation wicri:level="3"><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, INSERM U944 CNRS 7212, Hôpital Saint-Louis, 75010 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Paris, Institut de Recherche Saint-Louis, INSERM U944 CNRS 7212, Hôpital Saint-Louis, 75010 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Soumelis, Vassili" sort="Soumelis, Vassili" uniqKey="Soumelis V" first="Vassili" last="Soumelis">Vassili Soumelis</name><affiliation wicri:level="3"><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, INSERM U976, Hôpital Saint-Louis, 75010 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Paris, Institut de Recherche Saint-Louis, INSERM U976, Hôpital Saint-Louis, 75010 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis, Laboratoire d'Immunologie, F-75010, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis, Laboratoire d'Immunologie, F-75010, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2021">2021</date><idno type="RBID">pubmed:33442685</idno><idno type="pmid">33442685</idno><idno type="doi">10.1101/2020.07.10.197343</idno><idno type="pmc">PMC7805442</idno><idno type="wicri:Area/Main/Corpus">000489</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000489</idno><idno type="wicri:Area/Main/Curation">000489</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000489</idno><idno type="wicri:Area/Main/Exploration">000489</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">SARS-CoV-2 induces human plasmacytoid pre-dendritic cell diversification via UNC93B and IRAK4.</title><author><name sortKey="Onodi, Fanny" sort="Onodi, Fanny" uniqKey="Onodi F" first="Fanny" last="Onodi">Fanny Onodi</name><affiliation wicri:level="3"><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, INSERM U976, Hôpital Saint-Louis, 75010 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Paris, Institut de Recherche Saint-Louis, INSERM U976, Hôpital Saint-Louis, 75010 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Bonnet Madin, Lucie" sort="Bonnet Madin, Lucie" uniqKey="Bonnet Madin L" first="Lucie" last="Bonnet-Madin">Lucie Bonnet-Madin</name><affiliation wicri:level="3"><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, INSERM U944 CNRS 7212, Hôpital Saint-Louis, 75010 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Paris, Institut de Recherche Saint-Louis, INSERM U944 CNRS 7212, Hôpital Saint-Louis, 75010 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Meertens, Laurent" sort="Meertens, Laurent" uniqKey="Meertens L" first="Laurent" last="Meertens">Laurent Meertens</name><affiliation wicri:level="3"><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, INSERM U944 CNRS 7212, Hôpital Saint-Louis, 75010 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Paris, Institut de Recherche Saint-Louis, INSERM U944 CNRS 7212, Hôpital Saint-Louis, 75010 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Karpf, Lea" sort="Karpf, Lea" uniqKey="Karpf L" first="Léa" last="Karpf">Léa Karpf</name><affiliation wicri:level="3"><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, INSERM U976, Hôpital Saint-Louis, 75010 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Paris, Institut de Recherche Saint-Louis, INSERM U976, Hôpital Saint-Louis, 75010 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Poirot, Justine" sort="Poirot, Justine" uniqKey="Poirot J" first="Justine" last="Poirot">Justine Poirot</name><affiliation wicri:level="3"><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, INSERM U976, Hôpital Saint-Louis, 75010 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Paris, Institut de Recherche Saint-Louis, INSERM U976, Hôpital Saint-Louis, 75010 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Zhang, Shen Ying" sort="Zhang, Shen Ying" uniqKey="Zhang S" first="Shen-Ying" last="Zhang">Shen-Ying Zhang</name><affiliation><nlm:affiliation>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France, EU.</nlm:affiliation><wicri:noCountry code="subField">EU</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Université de Paris; INSERM UMR 1163 Institut Imagine, France EU.</nlm:affiliation><wicri:noCountry code="subField">France EU</wicri:noCountry></affiliation><affiliation wicri:level="2"><nlm:affiliation>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Picard, Capucine" sort="Picard, Capucine" uniqKey="Picard C" first="Capucine" last="Picard">Capucine Picard</name><affiliation><nlm:affiliation>Université de Paris; INSERM UMR 1163 Institut Imagine, France EU.</nlm:affiliation><wicri:noCountry code="subField">France EU</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Study center for primary immunodeficiencies, Necker Hospital for Sick Children Assistance Publique-Hôpitaux (AP-HP) de Paris, Paris, France, EU.</nlm:affiliation><wicri:noCountry code="subField">EU</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Pediatric Hematology and Immunology Unit, Necker Hospital for Sick Children, AP-HP, Paris, France, EU.</nlm:affiliation><wicri:noCountry code="subField">EU</wicri:noCountry></affiliation></author><author><name sortKey="Puel, Anne" sort="Puel, Anne" uniqKey="Puel A" first="Anne" last="Puel">Anne Puel</name><affiliation><nlm:affiliation>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France, EU.</nlm:affiliation><wicri:noCountry code="subField">EU</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Université de Paris; INSERM UMR 1163 Institut Imagine, France EU.</nlm:affiliation><wicri:noCountry code="subField">France EU</wicri:noCountry></affiliation><affiliation wicri:level="2"><nlm:affiliation>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Jouanguy, Emmanuelle" sort="Jouanguy, Emmanuelle" uniqKey="Jouanguy E" first="Emmanuelle" last="Jouanguy">Emmanuelle Jouanguy</name><affiliation><nlm:affiliation>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France, EU.</nlm:affiliation><wicri:noCountry code="subField">EU</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Université de Paris; INSERM UMR 1163 Institut Imagine, France EU.</nlm:affiliation><wicri:noCountry code="subField">France EU</wicri:noCountry></affiliation><affiliation wicri:level="2"><nlm:affiliation>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Zhang, Qian" sort="Zhang, Qian" uniqKey="Zhang Q" first="Qian" last="Zhang">Qian Zhang</name><affiliation wicri:level="2"><nlm:affiliation>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Le Goff, Jerome" sort="Le Goff, Jerome" uniqKey="Le Goff J" first="Jérôme" last="Le Goff">Jérôme Le Goff</name><affiliation wicri:level="3"><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, INSERM U976, Hôpital Saint-Louis, 75010 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Paris, Institut de Recherche Saint-Louis, INSERM U976, Hôpital Saint-Louis, 75010 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Laboratoire de Virologie et Département des Maladies Infectieuses, Hôpital Saint-Louis, APHP, 75010 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Virologie et Département des Maladies Infectieuses, Hôpital Saint-Louis, APHP, 75010 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Molina, Jean Michel" sort="Molina, Jean Michel" uniqKey="Molina J" first="Jean-Michel" last="Molina">Jean-Michel Molina</name><affiliation wicri:level="3"><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, INSERM U944 CNRS 7212, Hôpital Saint-Louis, 75010 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Paris, Institut de Recherche Saint-Louis, INSERM U944 CNRS 7212, Hôpital Saint-Louis, 75010 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Laboratoire de Virologie et Département des Maladies Infectieuses, Hôpital Saint-Louis, APHP, 75010 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Virologie et Département des Maladies Infectieuses, Hôpital Saint-Louis, APHP, 75010 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Delaugerre, Constance" sort="Delaugerre, Constance" uniqKey="Delaugerre C" first="Constance" last="Delaugerre">Constance Delaugerre</name><affiliation wicri:level="3"><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, INSERM U944 CNRS 7212, Hôpital Saint-Louis, 75010 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Paris, Institut de Recherche Saint-Louis, INSERM U944 CNRS 7212, Hôpital Saint-Louis, 75010 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Laboratoire de Virologie et Département des Maladies Infectieuses, Hôpital Saint-Louis, APHP, 75010 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Virologie et Département des Maladies Infectieuses, Hôpital Saint-Louis, APHP, 75010 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Casanova, Jean Laurent" sort="Casanova, Jean Laurent" uniqKey="Casanova J" first="Jean-Laurent" last="Casanova">Jean-Laurent Casanova</name><affiliation><nlm:affiliation>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France, EU.</nlm:affiliation><wicri:noCountry code="subField">EU</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Université de Paris; INSERM UMR 1163 Institut Imagine, France EU.</nlm:affiliation><wicri:noCountry code="subField">France EU</wicri:noCountry></affiliation><affiliation wicri:level="2"><nlm:affiliation>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation><affiliation><nlm:affiliation>Pediatric Hematology and Immunology Unit, Necker Hospital for Sick Children, AP-HP, Paris, France, EU.</nlm:affiliation><wicri:noCountry code="subField">EU</wicri:noCountry></affiliation><affiliation wicri:level="2"><nlm:affiliation>Howard Hughes Medical Institute, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Howard Hughes Medical Institute, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Amara, Ali" sort="Amara, Ali" uniqKey="Amara A" first="Ali" last="Amara">Ali Amara</name><affiliation wicri:level="3"><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, INSERM U944 CNRS 7212, Hôpital Saint-Louis, 75010 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Paris, Institut de Recherche Saint-Louis, INSERM U944 CNRS 7212, Hôpital Saint-Louis, 75010 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Soumelis, Vassili" sort="Soumelis, Vassili" uniqKey="Soumelis V" first="Vassili" last="Soumelis">Vassili Soumelis</name><affiliation wicri:level="3"><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, INSERM U976, Hôpital Saint-Louis, 75010 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Université de Paris, Institut de Recherche Saint-Louis, INSERM U976, Hôpital Saint-Louis, 75010 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation><affiliation wicri:level="3"><nlm:affiliation>Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis, Laboratoire d'Immunologie, F-75010, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis, Laboratoire d'Immunologie, F-75010, Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author></analytic><series><title level="j">bioRxiv : the preprint server for biology</title><imprint><date when="2021" type="published">2021</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">33442685</PMID><DateRevised><Year>2021</Year><Month>02</Month><Day>09</Day></DateRevised><Article PubModel="Electronic"><Journal><JournalIssue CitedMedium="Internet"><PubDate><Year>2021</Year><Month>Jan</Month><Day>08</Day></PubDate></JournalIssue><Title>bioRxiv : the preprint server for biology</Title><ISOAbbreviation>bioRxiv</ISOAbbreviation></Journal><ArticleTitle>SARS-CoV-2 induces human plasmacytoid pre-dendritic cell diversification via UNC93B and IRAK4.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">2020.07.10.197343</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1101/2020.07.10.197343</ELocationID><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Onodi</LastName><ForeName>Fanny</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Université de Paris, Institut de Recherche Saint-Louis, INSERM U976, Hôpital Saint-Louis, 75010 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bonnet-Madin</LastName><ForeName>Lucie</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Université de Paris, Institut de Recherche Saint-Louis, INSERM U944 CNRS 7212, Hôpital Saint-Louis, 75010 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Meertens</LastName><ForeName>Laurent</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Université de Paris, Institut de Recherche Saint-Louis, INSERM U944 CNRS 7212, Hôpital Saint-Louis, 75010 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Karpf</LastName><ForeName>Léa</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Université de Paris, Institut de Recherche Saint-Louis, INSERM U976, Hôpital Saint-Louis, 75010 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Poirot</LastName><ForeName>Justine</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Université de Paris, Institut de Recherche Saint-Louis, INSERM U976, Hôpital Saint-Louis, 75010 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Shen-Ying</ForeName><Initials>SY</Initials><AffiliationInfo><Affiliation>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France, EU.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Université de Paris; INSERM UMR 1163 Institut Imagine, France EU.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Picard</LastName><ForeName>Capucine</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Université de Paris; INSERM UMR 1163 Institut Imagine, France EU.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Study center for primary immunodeficiencies, Necker Hospital for Sick Children Assistance Publique-Hôpitaux (AP-HP) de Paris, Paris, France, EU.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Pediatric Hematology and Immunology Unit, Necker Hospital for Sick Children, AP-HP, Paris, France, EU.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Puel</LastName><ForeName>Anne</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France, EU.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Université de Paris; INSERM UMR 1163 Institut Imagine, France EU.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jouanguy</LastName><ForeName>Emmanuelle</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France, EU.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Université de Paris; INSERM UMR 1163 Institut Imagine, France EU.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Qian</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Le Goff</LastName><ForeName>Jérôme</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Université de Paris, Institut de Recherche Saint-Louis, INSERM U976, Hôpital Saint-Louis, 75010 Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Laboratoire de Virologie et Département des Maladies Infectieuses, Hôpital Saint-Louis, APHP, 75010 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Molina</LastName><ForeName>Jean-Michel</ForeName><Initials>JM</Initials><AffiliationInfo><Affiliation>Université de Paris, Institut de Recherche Saint-Louis, INSERM U944 CNRS 7212, Hôpital Saint-Louis, 75010 Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Laboratoire de Virologie et Département des Maladies Infectieuses, Hôpital Saint-Louis, APHP, 75010 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Delaugerre</LastName><ForeName>Constance</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Université de Paris, Institut de Recherche Saint-Louis, INSERM U944 CNRS 7212, Hôpital Saint-Louis, 75010 Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Laboratoire de Virologie et Département des Maladies Infectieuses, Hôpital Saint-Louis, APHP, 75010 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Casanova</LastName><ForeName>Jean-Laurent</ForeName><Initials>JL</Initials><AffiliationInfo><Affiliation>Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France, EU.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Université de Paris; INSERM UMR 1163 Institut Imagine, France EU.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Pediatric Hematology and Immunology Unit, Necker Hospital for Sick Children, AP-HP, Paris, France, EU.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Howard Hughes Medical Institute, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Amara</LastName><ForeName>Ali</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Université de Paris, Institut de Recherche Saint-Louis, INSERM U944 CNRS 7212, Hôpital Saint-Louis, 75010 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Soumelis</LastName><ForeName>Vassili</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Université de Paris, Institut de Recherche Saint-Louis, INSERM U976, Hôpital Saint-Louis, 75010 Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis, Laboratoire d'Immunologie, F-75010, Paris, France.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 AI088364</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>U24 HG008956</GrantID><Acronym>HG</Acronym><Agency>NHGRI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>UL1 TR001866</GrantID><Acronym>TR</Acronym><Agency>NCATS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>UM1 HG006504</GrantID><Acronym>HG</Acronym><Agency>NHGRI NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D000076942">Preprint</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2021</Year><Month>01</Month><Day>08</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>bioRxiv</MedlineTA><NlmUniqueID>101680187</NlmUniqueID></MedlineJournalInfo><CommentsCorrectionsList><CommentsCorrections RefType="UpdateIn"><RefSource>J Exp Med. 2021 Apr 5;218(4):</RefSource><PMID Version="1">33533916</PMID></CommentsCorrections></CommentsCorrectionsList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2021</Year><Month>1</Month><Day>14</Day><Hour>5</Hour><Minute>48</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2021</Year><Month>1</Month><Day>15</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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IdType="pubmed">32442210</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></pubmed><affiliations><list><country><li>France</li><li>États-Unis</li></country><region><li>État de New York</li><li>Île-de-France</li></region><settlement><li>Paris</li></settlement></list><tree><noCountry><name sortKey="Picard, Capucine" sort="Picard, Capucine" uniqKey="Picard C" first="Capucine" last="Picard">Capucine Picard</name></noCountry><country name="France"><region name="Île-de-France"><name sortKey="Onodi, Fanny" sort="Onodi, Fanny" uniqKey="Onodi F" first="Fanny" last="Onodi">Fanny Onodi</name></region><name sortKey="Amara, Ali" sort="Amara, Ali" uniqKey="Amara A" first="Ali" last="Amara">Ali Amara</name><name sortKey="Bonnet Madin, Lucie" sort="Bonnet Madin, Lucie" uniqKey="Bonnet Madin L" first="Lucie" last="Bonnet-Madin">Lucie Bonnet-Madin</name><name sortKey="Delaugerre, Constance" sort="Delaugerre, Constance" uniqKey="Delaugerre C" first="Constance" last="Delaugerre">Constance Delaugerre</name><name sortKey="Delaugerre, Constance" sort="Delaugerre, Constance" uniqKey="Delaugerre C" first="Constance" last="Delaugerre">Constance Delaugerre</name><name sortKey="Karpf, Lea" sort="Karpf, Lea" uniqKey="Karpf L" first="Léa" last="Karpf">Léa Karpf</name><name sortKey="Le Goff, Jerome" sort="Le Goff, Jerome" uniqKey="Le Goff J" first="Jérôme" last="Le Goff">Jérôme Le Goff</name><name sortKey="Le Goff, Jerome" sort="Le Goff, Jerome" uniqKey="Le Goff J" first="Jérôme" last="Le Goff">Jérôme Le Goff</name><name sortKey="Meertens, Laurent" sort="Meertens, Laurent" uniqKey="Meertens L" first="Laurent" last="Meertens">Laurent Meertens</name><name sortKey="Molina, Jean Michel" sort="Molina, Jean Michel" uniqKey="Molina J" first="Jean-Michel" last="Molina">Jean-Michel Molina</name><name sortKey="Molina, Jean Michel" sort="Molina, Jean Michel" uniqKey="Molina J" first="Jean-Michel" last="Molina">Jean-Michel Molina</name><name sortKey="Poirot, Justine" sort="Poirot, Justine" uniqKey="Poirot J" first="Justine" last="Poirot">Justine Poirot</name><name sortKey="Soumelis, Vassili" sort="Soumelis, Vassili" uniqKey="Soumelis V" first="Vassili" last="Soumelis">Vassili Soumelis</name><name sortKey="Soumelis, Vassili" sort="Soumelis, Vassili" uniqKey="Soumelis V" first="Vassili" last="Soumelis">Vassili Soumelis</name></country><country name="États-Unis"><region name="État de New York"><name sortKey="Zhang, Shen Ying" sort="Zhang, Shen Ying" uniqKey="Zhang S" first="Shen-Ying" last="Zhang">Shen-Ying Zhang</name></region><name sortKey="Casanova, Jean Laurent" sort="Casanova, Jean Laurent" uniqKey="Casanova J" first="Jean-Laurent" last="Casanova">Jean-Laurent Casanova</name><name sortKey="Casanova, Jean Laurent" sort="Casanova, Jean Laurent" uniqKey="Casanova J" first="Jean-Laurent" last="Casanova">Jean-Laurent Casanova</name><name sortKey="Jouanguy, Emmanuelle" sort="Jouanguy, Emmanuelle" uniqKey="Jouanguy E" first="Emmanuelle" last="Jouanguy">Emmanuelle Jouanguy</name><name sortKey="Puel, Anne" sort="Puel, Anne" uniqKey="Puel A" first="Anne" last="Puel">Anne Puel</name><name sortKey="Zhang, Qian" sort="Zhang, Qian" uniqKey="Zhang Q" first="Qian" last="Zhang">Qian Zhang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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