SARS-CoV-2 induces human plasmacytoid predendritic cell diversification via UNC93B and IRAK4.
Identifieur interne : 000396 ( Main/Corpus ); précédent : 000395; suivant : 000397SARS-CoV-2 induces human plasmacytoid predendritic cell diversification via UNC93B and IRAK4.
Auteurs : 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 SoumelisSource :
- The Journal of experimental medicine [ 1540-9538 ] ; 2021.
English descriptors
- KwdEn :
- Biomarkers (MeSH), COVID-19 (drug therapy), COVID-19 (immunology), COVID-19 (metabolism), COVID-19 (virology), Cell Plasticity (immunology), Cytokines (metabolism), Dendritic Cells (immunology), Dendritic Cells (metabolism), Dendritic Cells (virology), Host-Pathogen Interactions (immunology), Humans (MeSH), Hydroxychloroquine (pharmacology), Hydroxychloroquine (therapeutic use), Immunomodulation (MeSH), Immunophenotyping (MeSH), Inflammation Mediators (metabolism), Interferon Type I (metabolism), Interferons (metabolism), Interleukin-1 Receptor-Associated Kinases (metabolism), Membrane Transport Proteins (metabolism), SARS-CoV-2 (immunology).
- MESH :
- chemical , metabolism : Cytokines, Inflammation Mediators, Interferon Type I, Interferons, Interleukin-1 Receptor-Associated Kinases, Membrane Transport Proteins.
- chemical , pharmacology : Hydroxychloroquine.
- chemical , therapeutic use : Hydroxychloroquine.
- chemical : Biomarkers.
- drug therapy : COVID-19.
- immunology : COVID-19, Cell Plasticity, Dendritic Cells, Host-Pathogen Interactions, SARS-CoV-2.
- metabolism : COVID-19, Dendritic Cells.
- virology : COVID-19, Dendritic Cells.
- Humans, Immunomodulation, Immunophenotyping.
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 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.
DOI: 10.1084/jem.20201387
PubMed: 33533916
PubMed Central: PMC7849819
Links to Exploration step
pubmed:33533916Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">SARS-CoV-2 induces human plasmacytoid predendritic 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><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, Institut National de la Santé et de la Recherche Médicale U976, Hôpital Saint-Louis, Paris, France.</nlm:affiliation></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><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, Institut National de la Santé et de la Recherche Médicale U944, Centre National de la Recherche Scientifique 7212, Hôpital Saint-Louis, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Meertens, Laurent" sort="Meertens, Laurent" uniqKey="Meertens L" first="Laurent" last="Meertens">Laurent Meertens</name><affiliation><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, Institut National de la Santé et de la Recherche Médicale U944, Centre National de la Recherche Scientifique 7212, Hôpital Saint-Louis, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Karpf, Lea" sort="Karpf, Lea" uniqKey="Karpf L" first="Léa" last="Karpf">Léa Karpf</name><affiliation><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, Institut National de la Santé et de la Recherche Médicale U976, Hôpital Saint-Louis, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Poirot, Justine" sort="Poirot, Justine" uniqKey="Poirot J" first="Justine" last="Poirot">Justine Poirot</name><affiliation><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, Institut National de la Santé et de la Recherche Médicale U976, Hôpital Saint-Louis, Paris, France.</nlm:affiliation></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, Institut National de la Santé et de la Recherche Médicale, Necker Hospital for Sick Children, Paris, France.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Université de Paris, Institut National de la Santé et de la Recherche Médicale Unite Mixte de Recherche 1163, Institut Imagine, Paris, France.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.</nlm:affiliation></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, Institut National de la Santé et de la Recherche Médicale Unite Mixte de Recherche 1163, Institut Imagine, Paris, France.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris, Paris, France.</nlm:affiliation></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, Institut National de la Santé et de la Recherche Médicale, Necker Hospital for Sick Children, Paris, France.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Université de Paris, Institut National de la Santé et de la Recherche Médicale Unite Mixte de Recherche 1163, Institut Imagine, Paris, France.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.</nlm:affiliation></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, Institut National de la Santé et de la Recherche Médicale, Necker Hospital for Sick Children, Paris, France.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Université de Paris, Institut National de la Santé et de la Recherche Médicale Unite Mixte de Recherche 1163, Institut Imagine, Paris, France.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.</nlm:affiliation></affiliation></author><author><name sortKey="Zhang, Qian" sort="Zhang, Qian" uniqKey="Zhang Q" first="Qian" last="Zhang">Qian Zhang</name><affiliation><nlm:affiliation>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.</nlm:affiliation></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><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, Institut National de la Santé et de la Recherche Médicale U976, Hôpital Saint-Louis, Paris, France.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Laboratoire de Virologie et Département des Maladies Infectieuses, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France.</nlm:affiliation></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><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, Institut National de la Santé et de la Recherche Médicale U944, Centre National de la Recherche Scientifique 7212, Hôpital Saint-Louis, Paris, France.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Laboratoire de Virologie et Département des Maladies Infectieuses, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Delaugerre, Constance" sort="Delaugerre, Constance" uniqKey="Delaugerre C" first="Constance" last="Delaugerre">Constance Delaugerre</name><affiliation><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, Institut National de la Santé et de la Recherche Médicale U944, Centre National de la Recherche Scientifique 7212, Hôpital Saint-Louis, Paris, France.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Laboratoire de Virologie et Département des Maladies Infectieuses, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France.</nlm:affiliation></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, Institut National de la Santé et de la Recherche Médicale, Necker Hospital for Sick Children, Paris, France.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Université de Paris, Institut National de la Santé et de la Recherche Médicale Unite Mixte de Recherche 1163, Institut Imagine, Paris, France.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Howard Hughes Medical Institute, New York, NY.</nlm:affiliation></affiliation></author><author><name sortKey="Amara, Ali" sort="Amara, Ali" uniqKey="Amara A" first="Ali" last="Amara">Ali Amara</name><affiliation><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, Institut National de la Santé et de la Recherche Médicale U944, Centre National de la Recherche Scientifique 7212, Hôpital Saint-Louis, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Soumelis, Vassili" sort="Soumelis, Vassili" uniqKey="Soumelis V" first="Vassili" last="Soumelis">Vassili Soumelis</name><affiliation><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, Institut National de la Santé et de la Recherche Médicale U976, Hôpital Saint-Louis, Paris, France.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Laboratoire d'Immunologie, Paris, France.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2021">2021</date><idno type="RBID">pubmed:33533916</idno><idno type="pmid">33533916</idno><idno type="doi">10.1084/jem.20201387</idno><idno type="pmc">PMC7849819</idno><idno type="wicri:Area/Main/Corpus">000396</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000396</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">SARS-CoV-2 induces human plasmacytoid predendritic 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><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, Institut National de la Santé et de la Recherche Médicale U976, Hôpital Saint-Louis, Paris, France.</nlm:affiliation></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><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, Institut National de la Santé et de la Recherche Médicale U944, Centre National de la Recherche Scientifique 7212, Hôpital Saint-Louis, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Meertens, Laurent" sort="Meertens, Laurent" uniqKey="Meertens L" first="Laurent" last="Meertens">Laurent Meertens</name><affiliation><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, Institut National de la Santé et de la Recherche Médicale U944, Centre National de la Recherche Scientifique 7212, Hôpital Saint-Louis, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Karpf, Lea" sort="Karpf, Lea" uniqKey="Karpf L" first="Léa" last="Karpf">Léa Karpf</name><affiliation><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, Institut National de la Santé et de la Recherche Médicale U976, Hôpital Saint-Louis, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Poirot, Justine" sort="Poirot, Justine" uniqKey="Poirot J" first="Justine" last="Poirot">Justine Poirot</name><affiliation><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, Institut National de la Santé et de la Recherche Médicale U976, Hôpital Saint-Louis, Paris, France.</nlm:affiliation></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, Institut National de la Santé et de la Recherche Médicale, Necker Hospital for Sick Children, Paris, France.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Université de Paris, Institut National de la Santé et de la Recherche Médicale Unite Mixte de Recherche 1163, Institut Imagine, Paris, France.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.</nlm:affiliation></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, Institut National de la Santé et de la Recherche Médicale Unite Mixte de Recherche 1163, Institut Imagine, Paris, France.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris, Paris, France.</nlm:affiliation></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, Institut National de la Santé et de la Recherche Médicale, Necker Hospital for Sick Children, Paris, France.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Université de Paris, Institut National de la Santé et de la Recherche Médicale Unite Mixte de Recherche 1163, Institut Imagine, Paris, France.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.</nlm:affiliation></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, Institut National de la Santé et de la Recherche Médicale, Necker Hospital for Sick Children, Paris, France.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Université de Paris, Institut National de la Santé et de la Recherche Médicale Unite Mixte de Recherche 1163, Institut Imagine, Paris, France.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.</nlm:affiliation></affiliation></author><author><name sortKey="Zhang, Qian" sort="Zhang, Qian" uniqKey="Zhang Q" first="Qian" last="Zhang">Qian Zhang</name><affiliation><nlm:affiliation>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.</nlm:affiliation></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><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, Institut National de la Santé et de la Recherche Médicale U976, Hôpital Saint-Louis, Paris, France.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Laboratoire de Virologie et Département des Maladies Infectieuses, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France.</nlm:affiliation></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><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, Institut National de la Santé et de la Recherche Médicale U944, Centre National de la Recherche Scientifique 7212, Hôpital Saint-Louis, Paris, France.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Laboratoire de Virologie et Département des Maladies Infectieuses, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Delaugerre, Constance" sort="Delaugerre, Constance" uniqKey="Delaugerre C" first="Constance" last="Delaugerre">Constance Delaugerre</name><affiliation><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, Institut National de la Santé et de la Recherche Médicale U944, Centre National de la Recherche Scientifique 7212, Hôpital Saint-Louis, Paris, France.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Laboratoire de Virologie et Département des Maladies Infectieuses, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France.</nlm:affiliation></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, Institut National de la Santé et de la Recherche Médicale, Necker Hospital for Sick Children, Paris, France.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Université de Paris, Institut National de la Santé et de la Recherche Médicale Unite Mixte de Recherche 1163, Institut Imagine, Paris, France.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Howard Hughes Medical Institute, New York, NY.</nlm:affiliation></affiliation></author><author><name sortKey="Amara, Ali" sort="Amara, Ali" uniqKey="Amara A" first="Ali" last="Amara">Ali Amara</name><affiliation><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, Institut National de la Santé et de la Recherche Médicale U944, Centre National de la Recherche Scientifique 7212, Hôpital Saint-Louis, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Soumelis, Vassili" sort="Soumelis, Vassili" uniqKey="Soumelis V" first="Vassili" last="Soumelis">Vassili Soumelis</name><affiliation><nlm:affiliation>Université de Paris, Institut de Recherche Saint-Louis, Institut National de la Santé et de la Recherche Médicale U976, Hôpital Saint-Louis, Paris, France.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Laboratoire d'Immunologie, Paris, France.</nlm:affiliation></affiliation></author></analytic><series><title level="j">The Journal of experimental medicine</title><idno type="eISSN">1540-9538</idno><imprint><date when="2021" type="published">2021</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Biomarkers (MeSH)</term><term>COVID-19 (drug therapy)</term><term>COVID-19 (immunology)</term><term>COVID-19 (metabolism)</term><term>COVID-19 (virology)</term><term>Cell Plasticity (immunology)</term><term>Cytokines (metabolism)</term><term>Dendritic Cells (immunology)</term><term>Dendritic Cells (metabolism)</term><term>Dendritic Cells (virology)</term><term>Host-Pathogen Interactions (immunology)</term><term>Humans (MeSH)</term><term>Hydroxychloroquine (pharmacology)</term><term>Hydroxychloroquine (therapeutic use)</term><term>Immunomodulation (MeSH)</term><term>Immunophenotyping (MeSH)</term><term>Inflammation Mediators (metabolism)</term><term>Interferon Type I (metabolism)</term><term>Interferons (metabolism)</term><term>Interleukin-1 Receptor-Associated Kinases (metabolism)</term><term>Membrane Transport Proteins (metabolism)</term><term>SARS-CoV-2 (immunology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cytokines</term><term>Inflammation Mediators</term><term>Interferon Type I</term><term>Interferons</term><term>Interleukin-1 Receptor-Associated Kinases</term><term>Membrane Transport Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Hydroxychloroquine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Hydroxychloroquine</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Biomarkers</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>COVID-19</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>COVID-19</term><term>Cell Plasticity</term><term>Dendritic Cells</term><term>Host-Pathogen Interactions</term><term>SARS-CoV-2</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>COVID-19</term><term>Dendritic Cells</term></keywords><keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>COVID-19</term><term>Dendritic Cells</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Humans</term><term>Immunomodulation</term><term>Immunophenotyping</term></keywords></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 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.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">33533916</PMID><DateCompleted><Year>2021</Year><Month>02</Month><Day>10</Day></DateCompleted><DateRevised><Year>2021</Year><Month>05</Month><Day>14</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1540-9538</ISSN><JournalIssue CitedMedium="Internet"><Volume>218</Volume><Issue>4</Issue><PubDate><Year>2021</Year><Month>04</Month><Day>05</Day></PubDate></JournalIssue><Title>The Journal of experimental medicine</Title><ISOAbbreviation>J Exp Med</ISOAbbreviation></Journal><ArticleTitle>SARS-CoV-2 induces human plasmacytoid predendritic cell diversification via UNC93B and IRAK4.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">e20201387</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1084/jem.20201387</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 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.</AbstractText><CopyrightInformation>© 2021 Onodi et al.</CopyrightInformation></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, Institut National de la Santé et de la Recherche Médicale U976, Hôpital Saint-Louis, 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, Institut National de la Santé et de la Recherche Médicale U944, Centre National de la Recherche Scientifique 7212, Hôpital Saint-Louis, 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, Institut National de la Santé et de la Recherche Médicale U944, Centre National de la Recherche Scientifique 7212, Hôpital Saint-Louis, 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, Institut National de la Santé et de la Recherche Médicale U976, Hôpital Saint-Louis, 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, Institut National de la Santé et de la Recherche Médicale U976, Hôpital Saint-Louis, 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, Institut National de la Santé et de la Recherche Médicale, Necker Hospital for Sick Children, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Université de Paris, Institut National de la Santé et de la Recherche Médicale Unite Mixte de Recherche 1163, Institut Imagine, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Picard</LastName><ForeName>Capucine</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Université de Paris, Institut National de la Santé et de la Recherche Médicale Unite Mixte de Recherche 1163, Institut Imagine, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Study Center for Primary Immunodeficiencies, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris, Paris, France.</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, Institut National de la Santé et de la Recherche Médicale, Necker Hospital for Sick Children, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Université de Paris, Institut National de la Santé et de la Recherche Médicale Unite Mixte de Recherche 1163, Institut Imagine, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.</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, Institut National de la Santé et de la Recherche Médicale, Necker Hospital for Sick Children, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Université de Paris, Institut National de la Santé et de la Recherche Médicale Unite Mixte de Recherche 1163, Institut Imagine, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.</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.</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, Institut National de la Santé et de la Recherche Médicale U976, Hôpital Saint-Louis, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Laboratoire de Virologie et Département des Maladies Infectieuses, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, 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, Institut National de la Santé et de la Recherche Médicale U944, Centre National de la Recherche Scientifique 7212, Hôpital Saint-Louis, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Laboratoire de Virologie et Département des Maladies Infectieuses, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, 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, Institut National de la Santé et de la Recherche Médicale U944, Centre National de la Recherche Scientifique 7212, Hôpital Saint-Louis, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Laboratoire de Virologie et Département des Maladies Infectieuses, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, 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, Institut National de la Santé et de la Recherche Médicale, Necker Hospital for Sick Children, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Université de Paris, Institut National de la Santé et de la Recherche Médicale Unite Mixte de Recherche 1163, Institut Imagine, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Howard Hughes Medical Institute, New York, NY.</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, Institut National de la Santé et de la Recherche Médicale U944, Centre National de la Recherche Scientifique 7212, Hôpital Saint-Louis, 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, Institut National de la Santé et de la Recherche Médicale U976, Hôpital Saint-Louis, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Laboratoire d'Immunologie, 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="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Exp Med</MedlineTA><NlmUniqueID>2985109R</NlmUniqueID><ISSNLinking>0022-1007</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D015415">Biomarkers</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D016207">Cytokines</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018836">Inflammation Mediators</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D007370">Interferon Type I</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D026901">Membrane Transport Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C454130">UNC93B1 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C000627197">interferon type III</NameOfSubstance></Chemical><Chemical><RegistryNumber>4QWG6N8QKH</RegistryNumber><NameOfSubstance UI="D006886">Hydroxychloroquine</NameOfSubstance></Chemical><Chemical><RegistryNumber>9008-11-1</RegistryNumber><NameOfSubstance UI="D007372">Interferons</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="C507773">IRAK4 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="D053592">Interleukin-1 Receptor-Associated Kinases</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="UpdateOf"><RefSource>bioRxiv. 2021 Jan 08;:</RefSource><PMID Version="1">33442685</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D015415" MajorTopicYN="N">Biomarkers</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000086382" MajorTopicYN="N">COVID-19</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName><QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000066670" MajorTopicYN="N">Cell Plasticity</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016207" MajorTopicYN="N">Cytokines</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D003713" MajorTopicYN="N">Dendritic Cells</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName><QualifierName UI="Q000821" MajorTopicYN="N">virology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D054884" MajorTopicYN="N">Host-Pathogen Interactions</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006886" MajorTopicYN="N">Hydroxychloroquine</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D056747" MajorTopicYN="N">Immunomodulation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D016130" MajorTopicYN="N">Immunophenotyping</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D018836" MajorTopicYN="N">Inflammation Mediators</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007370" MajorTopicYN="N">Interferon Type I</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007372" MajorTopicYN="N">Interferons</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D053592" MajorTopicYN="N">Interleukin-1 Receptor-Associated Kinases</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D026901" MajorTopicYN="N">Membrane Transport Proteins</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000086402" MajorTopicYN="N">SARS-CoV-2</DescriptorName><QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName></MeshHeading></MeshHeadingList><CoiStatement>Disclosures: J.-M. Molina reported grants from Gilead and personal fees from Merck, ViiV, and Janssen outside the submitted work. V. Soumelis reported grants from Sanofi and Roche, and personal fees from Leo Pharma, Gilead, Merck, and Sanofi outside the submitted work. No other disclosures were reported.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>07</Month><Day>01</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2020</Year><Month>10</Month><Day>08</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2021</Year><Month>01</Month><Day>07</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2021</Year><Month>2</Month><Day>3</Day><Hour>12</Hour><Minute>13</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2021</Year><Month>2</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2021</Year><Month>2</Month><Day>11</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">33533916</ArticleId><ArticleId IdType="pii">211734</ArticleId><ArticleId IdType="doi">10.1084/jem.20201387</ArticleId><ArticleId 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