Hydroxychloroquine Inhibits the Trained Innate Immune Response to Interferons.
Identifieur interne : 000580 ( Main/Corpus ); précédent : 000579; suivant : 000581Hydroxychloroquine Inhibits the Trained Innate Immune Response to Interferons.
Auteurs : Nils Rother ; Cansu Yanginlar ; Rik G H. Lindeboom ; Siroon Bekkering ; Mandy M T. Van Leent ; Baranca Buijsers ; Inge Jonkman ; Mark De Graaf ; Marijke Baltissen ; Lieke A. Lamers ; Niels P. Riksen ; Zahi A. Fayad ; Willem J M. Mulder ; Luuk B. Hilbrands ; Leo A B. Joosten ; Mihai G. Netea ; Michiel Vermeulen ; Johan Van Der Vlag ; Raphaël DuivenvoordenSource :
- Cell reports. Medicine [ 2666-3791 ] ; 2020.
Abstract
Hydroxychloroquine is being investigated for a potential prophylactic effect in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but its mechanism of action is poorly understood. Circulating leukocytes from the blood of coronavirus disease 2019 (COVID-19) patients show increased responses to Toll-like receptor ligands, suggestive of trained immunity. By analyzing interferon responses of peripheral blood mononuclear cells from healthy donors conditioned with heat-killed Candida, trained innate immunity can be modeled in vitro. In this model, hydroxychloroquine inhibits the responsiveness of these innate immune cells to virus-like stimuli and interferons. This is associated with a suppression of histone 3 lysine 27 acetylation and histone 3 lysine 4 trimethylation of inflammation-related genes, changes in the cellular lipidome, and decreased expression of interferon-stimulated genes. Our findings indicate that hydroxychloroquine inhibits trained immunity in vitro, which may not be beneficial for the antiviral innate immune response to SARS-CoV-2 infection in patients.
DOI: 10.1016/j.xcrm.2020.100146
PubMed: 33377122
PubMed Central: PMC7762774
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Hydroxychloroquine Inhibits the Trained Innate Immune Response to Interferons.</title><author><name sortKey="Rother, Nils" sort="Rother, Nils" uniqKey="Rother N" first="Nils" last="Rother">Nils Rother</name><affiliation><nlm:affiliation>Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Yanginlar, Cansu" sort="Yanginlar, Cansu" uniqKey="Yanginlar C" first="Cansu" last="Yanginlar">Cansu Yanginlar</name><affiliation><nlm:affiliation>Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Lindeboom, Rik G H" sort="Lindeboom, Rik G H" uniqKey="Lindeboom R" first="Rik G H" last="Lindeboom">Rik G H. Lindeboom</name><affiliation><nlm:affiliation>Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen, Nijmegen, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Bekkering, Siroon" sort="Bekkering, Siroon" uniqKey="Bekkering S" first="Siroon" last="Bekkering">Siroon Bekkering</name><affiliation><nlm:affiliation>Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Van Leent, Mandy M T" sort="Van Leent, Mandy M T" uniqKey="Van Leent M" first="Mandy M T" last="Van Leent">Mandy M T. Van Leent</name><affiliation><nlm:affiliation>Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department of Medical Biochemistry, Amsterdam University Medical Centers, Amsterdam, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Buijsers, Baranca" sort="Buijsers, Baranca" uniqKey="Buijsers B" first="Baranca" last="Buijsers">Baranca Buijsers</name><affiliation><nlm:affiliation>Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Jonkman, Inge" sort="Jonkman, Inge" uniqKey="Jonkman I" first="Inge" last="Jonkman">Inge Jonkman</name><affiliation><nlm:affiliation>Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="De Graaf, Mark" sort="De Graaf, Mark" uniqKey="De Graaf M" first="Mark" last="De Graaf">Mark De Graaf</name><affiliation><nlm:affiliation>Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Baltissen, Marijke" sort="Baltissen, Marijke" uniqKey="Baltissen M" first="Marijke" last="Baltissen">Marijke Baltissen</name><affiliation><nlm:affiliation>Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen, Nijmegen, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Lamers, Lieke A" sort="Lamers, Lieke A" uniqKey="Lamers L" first="Lieke A" last="Lamers">Lieke A. Lamers</name><affiliation><nlm:affiliation>Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen, Nijmegen, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Riksen, Niels P" sort="Riksen, Niels P" uniqKey="Riksen N" first="Niels P" last="Riksen">Niels P. Riksen</name><affiliation><nlm:affiliation>Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Fayad, Zahi A" sort="Fayad, Zahi A" uniqKey="Fayad Z" first="Zahi A" last="Fayad">Zahi A. Fayad</name><affiliation><nlm:affiliation>Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Mulder, Willem J M" sort="Mulder, Willem J M" uniqKey="Mulder W" first="Willem J M" last="Mulder">Willem J M. Mulder</name><affiliation><nlm:affiliation>Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Laboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, the Netherlands.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Hilbrands, Luuk B" sort="Hilbrands, Luuk B" uniqKey="Hilbrands L" first="Luuk B" last="Hilbrands">Luuk B. Hilbrands</name><affiliation><nlm:affiliation>Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Joosten, Leo A B" sort="Joosten, Leo A B" uniqKey="Joosten L" first="Leo A B" last="Joosten">Leo A B. Joosten</name><affiliation><nlm:affiliation>Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Netea, Mihai G" sort="Netea, Mihai G" uniqKey="Netea M" first="Mihai G" last="Netea">Mihai G. Netea</name><affiliation><nlm:affiliation>Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department of Immunology and Metabolism, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Vermeulen, Michiel" sort="Vermeulen, Michiel" uniqKey="Vermeulen M" first="Michiel" last="Vermeulen">Michiel Vermeulen</name><affiliation><nlm:affiliation>Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen, Nijmegen, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Van Der Vlag, Johan" sort="Van Der Vlag, Johan" uniqKey="Van Der Vlag J" first="Johan" last="Van Der Vlag">Johan Van Der Vlag</name><affiliation><nlm:affiliation>Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Duivenvoorden, Raphael" sort="Duivenvoorden, Raphael" uniqKey="Duivenvoorden R" first="Raphaël" last="Duivenvoorden">Raphaël Duivenvoorden</name><affiliation><nlm:affiliation>Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:33377122</idno><idno type="pmid">33377122</idno><idno type="doi">10.1016/j.xcrm.2020.100146</idno><idno type="pmc">PMC7762774</idno><idno type="wicri:Area/Main/Corpus">000580</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000580</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Hydroxychloroquine Inhibits the Trained Innate Immune Response to Interferons.</title><author><name sortKey="Rother, Nils" sort="Rother, Nils" uniqKey="Rother N" first="Nils" last="Rother">Nils Rother</name><affiliation><nlm:affiliation>Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Yanginlar, Cansu" sort="Yanginlar, Cansu" uniqKey="Yanginlar C" first="Cansu" last="Yanginlar">Cansu Yanginlar</name><affiliation><nlm:affiliation>Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Lindeboom, Rik G H" sort="Lindeboom, Rik G H" uniqKey="Lindeboom R" first="Rik G H" last="Lindeboom">Rik G H. Lindeboom</name><affiliation><nlm:affiliation>Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen, Nijmegen, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Bekkering, Siroon" sort="Bekkering, Siroon" uniqKey="Bekkering S" first="Siroon" last="Bekkering">Siroon Bekkering</name><affiliation><nlm:affiliation>Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Van Leent, Mandy M T" sort="Van Leent, Mandy M T" uniqKey="Van Leent M" first="Mandy M T" last="Van Leent">Mandy M T. Van Leent</name><affiliation><nlm:affiliation>Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department of Medical Biochemistry, Amsterdam University Medical Centers, Amsterdam, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Buijsers, Baranca" sort="Buijsers, Baranca" uniqKey="Buijsers B" first="Baranca" last="Buijsers">Baranca Buijsers</name><affiliation><nlm:affiliation>Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Jonkman, Inge" sort="Jonkman, Inge" uniqKey="Jonkman I" first="Inge" last="Jonkman">Inge Jonkman</name><affiliation><nlm:affiliation>Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="De Graaf, Mark" sort="De Graaf, Mark" uniqKey="De Graaf M" first="Mark" last="De Graaf">Mark De Graaf</name><affiliation><nlm:affiliation>Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Baltissen, Marijke" sort="Baltissen, Marijke" uniqKey="Baltissen M" first="Marijke" last="Baltissen">Marijke Baltissen</name><affiliation><nlm:affiliation>Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen, Nijmegen, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Lamers, Lieke A" sort="Lamers, Lieke A" uniqKey="Lamers L" first="Lieke A" last="Lamers">Lieke A. Lamers</name><affiliation><nlm:affiliation>Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen, Nijmegen, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Riksen, Niels P" sort="Riksen, Niels P" uniqKey="Riksen N" first="Niels P" last="Riksen">Niels P. Riksen</name><affiliation><nlm:affiliation>Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Fayad, Zahi A" sort="Fayad, Zahi A" uniqKey="Fayad Z" first="Zahi A" last="Fayad">Zahi A. Fayad</name><affiliation><nlm:affiliation>Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Mulder, Willem J M" sort="Mulder, Willem J M" uniqKey="Mulder W" first="Willem J M" last="Mulder">Willem J M. Mulder</name><affiliation><nlm:affiliation>Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Laboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, the Netherlands.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Hilbrands, Luuk B" sort="Hilbrands, Luuk B" uniqKey="Hilbrands L" first="Luuk B" last="Hilbrands">Luuk B. Hilbrands</name><affiliation><nlm:affiliation>Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Joosten, Leo A B" sort="Joosten, Leo A B" uniqKey="Joosten L" first="Leo A B" last="Joosten">Leo A B. Joosten</name><affiliation><nlm:affiliation>Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Netea, Mihai G" sort="Netea, Mihai G" uniqKey="Netea M" first="Mihai G" last="Netea">Mihai G. Netea</name><affiliation><nlm:affiliation>Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Department of Immunology and Metabolism, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Vermeulen, Michiel" sort="Vermeulen, Michiel" uniqKey="Vermeulen M" first="Michiel" last="Vermeulen">Michiel Vermeulen</name><affiliation><nlm:affiliation>Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen, Nijmegen, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Van Der Vlag, Johan" sort="Van Der Vlag, Johan" uniqKey="Van Der Vlag J" first="Johan" last="Van Der Vlag">Johan Van Der Vlag</name><affiliation><nlm:affiliation>Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Duivenvoorden, Raphael" sort="Duivenvoorden, Raphael" uniqKey="Duivenvoorden R" first="Raphaël" last="Duivenvoorden">Raphaël Duivenvoorden</name><affiliation><nlm:affiliation>Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</nlm:affiliation></affiliation><affiliation><nlm:affiliation>Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Cell reports. Medicine</title><idno type="eISSN">2666-3791</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Hydroxychloroquine is being investigated for a potential prophylactic effect in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but its mechanism of action is poorly understood. Circulating leukocytes from the blood of coronavirus disease 2019 (COVID-19) patients show increased responses to Toll-like receptor ligands, suggestive of trained immunity. By analyzing interferon responses of peripheral blood mononuclear cells from healthy donors conditioned with heat-killed <i>Candida</i>, trained innate immunity can be modeled <i>in vitro</i>. In this model, hydroxychloroquine inhibits the responsiveness of these innate immune cells to virus-like stimuli and interferons. This is associated with a suppression of histone 3 lysine 27 acetylation and histone 3 lysine 4 trimethylation of inflammation-related genes, changes in the cellular lipidome, and decreased expression of interferon-stimulated genes. Our findings indicate that hydroxychloroquine inhibits trained immunity <i>in vitro</i>, which may not be beneficial for the antiviral innate immune response to SARS-CoV-2 infection in patients.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">33377122</PMID><DateRevised><Year>2020</Year><Month>12</Month><Day>31</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">2666-3791</ISSN><JournalIssue CitedMedium="Internet"><Volume>1</Volume><Issue>9</Issue><PubDate><Year>2020</Year><Month>Dec</Month><Day>22</Day></PubDate></JournalIssue><Title>Cell reports. Medicine</Title><ISOAbbreviation>Cell Rep Med</ISOAbbreviation></Journal><ArticleTitle>Hydroxychloroquine Inhibits the Trained Innate Immune Response to Interferons.</ArticleTitle><Pagination><MedlinePgn>100146</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.xcrm.2020.100146</ELocationID><Abstract><AbstractText>Hydroxychloroquine is being investigated for a potential prophylactic effect in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but its mechanism of action is poorly understood. Circulating leukocytes from the blood of coronavirus disease 2019 (COVID-19) patients show increased responses to Toll-like receptor ligands, suggestive of trained immunity. By analyzing interferon responses of peripheral blood mononuclear cells from healthy donors conditioned with heat-killed <i>Candida</i>, trained innate immunity can be modeled <i>in vitro</i>. In this model, hydroxychloroquine inhibits the responsiveness of these innate immune cells to virus-like stimuli and interferons. This is associated with a suppression of histone 3 lysine 27 acetylation and histone 3 lysine 4 trimethylation of inflammation-related genes, changes in the cellular lipidome, and decreased expression of interferon-stimulated genes. Our findings indicate that hydroxychloroquine inhibits trained immunity <i>in vitro</i>, which may not be beneficial for the antiviral innate immune response to SARS-CoV-2 infection in patients.</AbstractText><CopyrightInformation>© 2020 The Authors.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Rother</LastName><ForeName>Nils</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yanginlar</LastName><ForeName>Cansu</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lindeboom</LastName><ForeName>Rik G H</ForeName><Initials>RGH</Initials><AffiliationInfo><Affiliation>Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen, Nijmegen, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bekkering</LastName><ForeName>Siroon</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>van Leent</LastName><ForeName>Mandy M T</ForeName><Initials>MMT</Initials><AffiliationInfo><Affiliation>Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Medical Biochemistry, Amsterdam University Medical Centers, Amsterdam, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Buijsers</LastName><ForeName>Baranca</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jonkman</LastName><ForeName>Inge</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>de Graaf</LastName><ForeName>Mark</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Baltissen</LastName><ForeName>Marijke</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen, Nijmegen, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lamers</LastName><ForeName>Lieke A</ForeName><Initials>LA</Initials><AffiliationInfo><Affiliation>Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen, Nijmegen, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Riksen</LastName><ForeName>Niels P</ForeName><Initials>NP</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fayad</LastName><ForeName>Zahi A</ForeName><Initials>ZA</Initials><AffiliationInfo><Affiliation>Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mulder</LastName><ForeName>Willem J M</ForeName><Initials>WJM</Initials><AffiliationInfo><Affiliation>Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Laboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, the Netherlands.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hilbrands</LastName><ForeName>Luuk B</ForeName><Initials>LB</Initials><AffiliationInfo><Affiliation>Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Joosten</LastName><ForeName>Leo A B</ForeName><Initials>LAB</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Netea</LastName><ForeName>Mihai G</ForeName><Initials>MG</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Immunology and Metabolism, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vermeulen</LastName><ForeName>Michiel</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Oncode Institute, Radboud University Nijmegen, Nijmegen, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>van der Vlag</LastName><ForeName>Johan</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Duivenvoorden</LastName><ForeName>Raphaël</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>11</Month><Day>10</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Cell Rep Med</MedlineTA><NlmUniqueID>101766894</NlmUniqueID><ISSNLinking>2666-3791</ISSNLinking></MedlineJournalInfo><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">COVID-19</Keyword><Keyword MajorTopicYN="N">SARS-CoV-2</Keyword><Keyword MajorTopicYN="N">chloroquine</Keyword><Keyword MajorTopicYN="N">hydroxychloroquine</Keyword><Keyword MajorTopicYN="N">innate immune memory</Keyword><Keyword MajorTopicYN="N">interferon</Keyword><Keyword MajorTopicYN="N">lipidome</Keyword><Keyword MajorTopicYN="N">monocytes</Keyword><Keyword MajorTopicYN="N">trained immunity</Keyword></KeywordList><CoiStatement>The authors declare no competing interests.</CoiStatement></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2020</Year><Month>06</Month><Day>16</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2020</Year><Month>09</Month><Day>14</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>11</Month><Day>03</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>12</Month><Day>30</Day><Hour>5</Hour><Minute>23</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>12</Month><Day>31</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate 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