Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection.
Identifieur interne : 003024 ( Ncbi/Merge ); précédent : 003023; suivant : 003025Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection.
Auteurs : Li Liu [République populaire de Chine] ; Qiang Wei [République populaire de Chine] ; Qingqing Lin [République populaire de Chine] ; Jun Fang [République populaire de Chine] ; Haibo Wang [République populaire de Chine] ; Hauyee Kwok [République populaire de Chine] ; Hangying Tang [République populaire de Chine] ; Kenji Nishiura [République populaire de Chine] ; Jie Peng [République populaire de Chine] ; Zhiwu Tan [République populaire de Chine] ; Tongjin Wu [République populaire de Chine] ; Ka-Wai Cheung [République populaire de Chine] ; Kwok-Hung Chan [République populaire de Chine] ; Xavier Alvarez [États-Unis] ; Chuan Qin [République populaire de Chine] ; Andrew Lackner [États-Unis] ; Stanley Perlman [États-Unis] ; Kwok-Yung Yuen [République populaire de Chine] ; Zhiwei Chen [République populaire de Chine]Source :
- JCI insight [ 2379-3708 ] ; 2019.
Abstract
Newly emerging viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV), Middle Eastern respiratory syndrome CoVs (MERS-CoV), and H7N9, cause fatal acute lung injury (ALI) by driving hypercytokinemia and aggressive inflammation through mechanisms that remain elusive. In SARS-CoV/macaque models, we determined that anti-spike IgG (S-IgG), in productively infected lungs, causes severe ALI by skewing inflammation-resolving response. Alveolar macrophages underwent functional polarization in acutely infected macaques, demonstrating simultaneously both proinflammatory and wound-healing characteristics. The presence of S-IgG prior to viral clearance, however, abrogated wound-healing responses and promoted MCP1 and IL-8 production and proinflammatory monocyte/macrophage recruitment and accumulation. Critically, patients who eventually died of SARS (hereafter referred to as deceased patients) displayed similarly accumulated pulmonary proinflammatory, absence of wound-healing macrophages, and faster neutralizing antibody responses. Their sera enhanced SARS-CoV-induced MCP1 and IL-8 production by human monocyte-derived wound-healing macrophages, whereas blockade of FcγR reduced such effects. Our findings reveal a mechanism responsible for virus-mediated ALI, define a pathological consequence of viral specific antibody response, and provide a potential target for treatment of SARS-CoV or other virus-mediated lung injury.
DOI: 10.1172/jci.insight.123158
PubMed: 30830861
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Kong</wicri:noRegion></affiliation></author><author><name sortKey="Nishiura, Kenji" sort="Nishiura, Kenji" uniqKey="Nishiura K" first="Kenji" last="Nishiura">Kenji Nishiura</name><affiliation wicri:level="1"><nlm:affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Peng, Jie" sort="Peng, Jie" uniqKey="Peng J" first="Jie" last="Peng">Jie Peng</name><affiliation wicri:level="1"><nlm:affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Tan, Zhiwu" sort="Tan, Zhiwu" uniqKey="Tan Z" first="Zhiwu" last="Tan">Zhiwu Tan</name><affiliation wicri:level="1"><nlm:affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Wu, Tongjin" sort="Wu, Tongjin" uniqKey="Wu T" first="Tongjin" last="Wu">Tongjin Wu</name><affiliation wicri:level="1"><nlm:affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Cheung, Ka Wai" sort="Cheung, Ka Wai" uniqKey="Cheung K" first="Ka-Wai" last="Cheung">Ka-Wai Cheung</name><affiliation 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Chine</country><wicri:regionArea>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Alvarez, Xavier" sort="Alvarez, Xavier" uniqKey="Alvarez X" first="Xavier" last="Alvarez">Xavier Alvarez</name><affiliation wicri:level="2"><nlm:affiliation>Division of Comparative Pathology, Tulane National Primate Research Center, Covington, Louisiana, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Comparative Pathology, Tulane National Primate Research Center, Covington, Louisiana</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation></author><author><name sortKey="Qin, Chuan" sort="Qin, Chuan" uniqKey="Qin C" first="Chuan" last="Qin">Chuan Qin</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Lackner, Andrew" sort="Lackner, Andrew" uniqKey="Lackner A" first="Andrew" last="Lackner">Andrew Lackner</name><affiliation wicri:level="2"><nlm:affiliation>Division of Comparative Pathology, Tulane National Primate Research Center, Covington, Louisiana, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Comparative Pathology, Tulane National Primate Research Center, Covington, Louisiana</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation></author><author><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa</wicri:regionArea><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name><affiliation wicri:level="1"><nlm:affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Zhiwei" sort="Chen, Zhiwei" uniqKey="Chen Z" first="Zhiwei" last="Chen">Zhiwei Chen</name><affiliation wicri:level="1"><nlm:affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2019">2019</date><idno type="RBID">pubmed:30830861</idno><idno type="pmid">30830861</idno><idno type="doi">10.1172/jci.insight.123158</idno><idno type="wicri:Area/PubMed/Corpus">000926</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000926</idno><idno type="wicri:Area/PubMed/Curation">000926</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000926</idno><idno type="wicri:Area/PubMed/Checkpoint">000930</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000930</idno><idno type="wicri:Area/Ncbi/Merge">003024</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection.</title><author><name sortKey="Liu, Li" sort="Liu, Li" uniqKey="Liu L" first="Li" last="Liu">Li Liu</name><affiliation wicri:level="1"><nlm:affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Wei, Qiang" sort="Wei, Qiang" uniqKey="Wei Q" first="Qiang" last="Wei">Qiang Wei</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Lin, Qingqing" sort="Lin, Qingqing" uniqKey="Lin Q" first="Qingqing" last="Lin">Qingqing Lin</name><affiliation wicri:level="1"><nlm:affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Fang, Jun" sort="Fang, Jun" uniqKey="Fang J" first="Jun" last="Fang">Jun Fang</name><affiliation wicri:level="1"><nlm:affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Haibo" sort="Wang, Haibo" uniqKey="Wang H" first="Haibo" last="Wang">Haibo Wang</name><affiliation wicri:level="1"><nlm:affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Kwok, Hauyee" sort="Kwok, Hauyee" uniqKey="Kwok H" first="Hauyee" last="Kwok">Hauyee Kwok</name><affiliation wicri:level="1"><nlm:affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Tang, Hangying" sort="Tang, Hangying" uniqKey="Tang H" first="Hangying" last="Tang">Hangying Tang</name><affiliation wicri:level="1"><nlm:affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Nishiura, Kenji" sort="Nishiura, Kenji" uniqKey="Nishiura K" first="Kenji" last="Nishiura">Kenji Nishiura</name><affiliation wicri:level="1"><nlm:affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Peng, Jie" sort="Peng, Jie" uniqKey="Peng J" first="Jie" last="Peng">Jie Peng</name><affiliation wicri:level="1"><nlm:affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Tan, Zhiwu" sort="Tan, Zhiwu" uniqKey="Tan Z" first="Zhiwu" last="Tan">Zhiwu Tan</name><affiliation wicri:level="1"><nlm:affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Wu, Tongjin" sort="Wu, Tongjin" uniqKey="Wu T" first="Tongjin" last="Wu">Tongjin Wu</name><affiliation wicri:level="1"><nlm:affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Cheung, Ka Wai" sort="Cheung, Ka Wai" uniqKey="Cheung K" first="Ka-Wai" last="Cheung">Ka-Wai Cheung</name><affiliation wicri:level="1"><nlm:affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Chan, Kwok Hung" sort="Chan, Kwok Hung" uniqKey="Chan K" first="Kwok-Hung" last="Chan">Kwok-Hung Chan</name><affiliation wicri:level="1"><nlm:affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Alvarez, Xavier" sort="Alvarez, Xavier" uniqKey="Alvarez X" first="Xavier" last="Alvarez">Xavier Alvarez</name><affiliation wicri:level="2"><nlm:affiliation>Division of Comparative Pathology, Tulane National Primate Research Center, Covington, Louisiana, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Comparative Pathology, Tulane National Primate Research Center, Covington, Louisiana</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation></author><author><name sortKey="Qin, Chuan" sort="Qin, Chuan" uniqKey="Qin C" first="Chuan" last="Qin">Chuan Qin</name><affiliation wicri:level="3"><nlm:affiliation>Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Lackner, Andrew" sort="Lackner, Andrew" uniqKey="Lackner A" first="Andrew" last="Lackner">Andrew Lackner</name><affiliation wicri:level="2"><nlm:affiliation>Division of Comparative Pathology, Tulane National Primate Research Center, Covington, Louisiana, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Comparative Pathology, Tulane National Primate Research Center, Covington, Louisiana</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation></author><author><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name><affiliation wicri:level="4"><nlm:affiliation>Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa</wicri:regionArea><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name><affiliation wicri:level="1"><nlm:affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Zhiwei" sort="Chen, Zhiwei" uniqKey="Chen Z" first="Zhiwei" last="Chen">Zhiwei Chen</name><affiliation wicri:level="1"><nlm:affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong</wicri:regionArea><wicri:noRegion>Hong Kong</wicri:noRegion></affiliation></author></analytic><series><title level="j">JCI insight</title><idno type="eISSN">2379-3708</idno><imprint><date when="2019" type="published">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Newly emerging viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV), Middle Eastern respiratory syndrome CoVs (MERS-CoV), and H7N9, cause fatal acute lung injury (ALI) by driving hypercytokinemia and aggressive inflammation through mechanisms that remain elusive. In SARS-CoV/macaque models, we determined that anti-spike IgG (S-IgG), in productively infected lungs, causes severe ALI by skewing inflammation-resolving response. Alveolar macrophages underwent functional polarization in acutely infected macaques, demonstrating simultaneously both proinflammatory and wound-healing characteristics. The presence of S-IgG prior to viral clearance, however, abrogated wound-healing responses and promoted MCP1 and IL-8 production and proinflammatory monocyte/macrophage recruitment and accumulation. Critically, patients who eventually died of SARS (hereafter referred to as deceased patients) displayed similarly accumulated pulmonary proinflammatory, absence of wound-healing macrophages, and faster neutralizing antibody responses. Their sera enhanced SARS-CoV-induced MCP1 and IL-8 production by human monocyte-derived wound-healing macrophages, whereas blockade of FcγR reduced such effects. Our findings reveal a mechanism responsible for virus-mediated ALI, define a pathological consequence of viral specific antibody response, and provide a potential target for treatment of SARS-CoV or other virus-mediated lung injury.</div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">30830861</PMID><DateRevised><Year>2020</Year><Month>03</Month><Day>19</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">2379-3708</ISSN><JournalIssue CitedMedium="Internet"><Volume>4</Volume><Issue>4</Issue><PubDate><Year>2019</Year><Month>02</Month><Day>21</Day></PubDate></JournalIssue><Title>JCI insight</Title><ISOAbbreviation>JCI Insight</ISOAbbreviation></Journal><ArticleTitle>Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection.</ArticleTitle><ELocationID EIdType="doi" ValidYN="Y">10.1172/jci.insight.123158</ELocationID><ELocationID EIdType="pii" ValidYN="Y">123158</ELocationID><Abstract><AbstractText>Newly emerging viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV), Middle Eastern respiratory syndrome CoVs (MERS-CoV), and H7N9, cause fatal acute lung injury (ALI) by driving hypercytokinemia and aggressive inflammation through mechanisms that remain elusive. In SARS-CoV/macaque models, we determined that anti-spike IgG (S-IgG), in productively infected lungs, causes severe ALI by skewing inflammation-resolving response. Alveolar macrophages underwent functional polarization in acutely infected macaques, demonstrating simultaneously both proinflammatory and wound-healing characteristics. The presence of S-IgG prior to viral clearance, however, abrogated wound-healing responses and promoted MCP1 and IL-8 production and proinflammatory monocyte/macrophage recruitment and accumulation. Critically, patients who eventually died of SARS (hereafter referred to as deceased patients) displayed similarly accumulated pulmonary proinflammatory, absence of wound-healing macrophages, and faster neutralizing antibody responses. Their sera enhanced SARS-CoV-induced MCP1 and IL-8 production by human monocyte-derived wound-healing macrophages, whereas blockade of FcγR reduced such effects. Our findings reveal a mechanism responsible for virus-mediated ALI, define a pathological consequence of viral specific antibody response, and provide a potential target for treatment of SARS-CoV or other virus-mediated lung injury.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Li</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>HKU-AIDS Institute Shenzhen Research Laboratory and AIDS Clinical Research Laboratory, Shenzhen Key Laboratory of Infection and Immunity, Shenzhen Key Clinical Department of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wei</LastName><ForeName>Qiang</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lin</LastName><ForeName>Qingqing</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fang</LastName><ForeName>Jun</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Haibo</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kwok</LastName><ForeName>Hauyee</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tang</LastName><ForeName>Hangying</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nishiura</LastName><ForeName>Kenji</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Peng</LastName><ForeName>Jie</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tan</LastName><ForeName>Zhiwu</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wu</LastName><ForeName>Tongjin</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cheung</LastName><ForeName>Ka-Wai</ForeName><Initials>KW</Initials><AffiliationInfo><Affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chan</LastName><ForeName>Kwok-Hung</ForeName><Initials>KH</Initials><AffiliationInfo><Affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Alvarez</LastName><ForeName>Xavier</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Division of Comparative Pathology, Tulane National Primate Research Center, Covington, Louisiana, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Qin</LastName><ForeName>Chuan</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lackner</LastName><ForeName>Andrew</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Division of Comparative Pathology, Tulane National Primate Research Center, Covington, Louisiana, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Perlman</LastName><ForeName>Stanley</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yuen</LastName><ForeName>Kwok-Yung</ForeName><Initials>KY</Initials><AffiliationInfo><Affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Zhiwei</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Disease, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>HKU-AIDS Institute Shenzhen Research Laboratory and AIDS Clinical Research Laboratory, Shenzhen Key Laboratory of Infection and Immunity, Shenzhen Key Clinical Department of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 HL080211</GrantID><Acronym>HL</Acronym><Agency>NHLBI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P51 RR000164</GrantID><Acronym>RR</Acronym><Agency>NCRR NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P51 OD011104</GrantID><Acronym>OD</Acronym><Agency>NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 AI129269</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P01 AI060699</GrantID><Acronym>AI</Acronym><Agency>NIAID NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>02</Month><Day>21</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>JCI Insight</MedlineTA><NlmUniqueID>101676073</NlmUniqueID><ISSNLinking>2379-3708</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">Cytokines</Keyword><Keyword MajorTopicYN="Y">Immunoglobulins</Keyword><Keyword MajorTopicYN="Y">Infectious disease</Keyword><Keyword MajorTopicYN="Y">Macrophages</Keyword><Keyword MajorTopicYN="Y">Pulmonology</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2018</Year><Month>07</Month><Day>23</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>01</Month><Day>11</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2019</Year><Month>3</Month><Day>5</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2019</Year><Month>3</Month><Day>5</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2019</Year><Month>3</Month><Day>5</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">30830861</ArticleId><ArticleId 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last="Tan">Zhiwu Tan</name><name sortKey="Tang, Hangying" sort="Tang, Hangying" uniqKey="Tang H" first="Hangying" last="Tang">Hangying Tang</name><name sortKey="Wang, Haibo" sort="Wang, Haibo" uniqKey="Wang H" first="Haibo" last="Wang">Haibo Wang</name><name sortKey="Wei, Qiang" sort="Wei, Qiang" uniqKey="Wei Q" first="Qiang" last="Wei">Qiang Wei</name><name sortKey="Wu, Tongjin" sort="Wu, Tongjin" uniqKey="Wu T" first="Tongjin" last="Wu">Tongjin Wu</name><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name></country><country name="États-Unis"><region name="Louisiane"><name sortKey="Alvarez, Xavier" sort="Alvarez, Xavier" uniqKey="Alvarez X" first="Xavier" last="Alvarez">Xavier Alvarez</name></region><name sortKey="Lackner, Andrew" sort="Lackner, Andrew" uniqKey="Lackner A" first="Andrew" last="Lackner">Andrew Lackner</name><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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