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Article: Anti–spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection

TitleAnti–spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection
Authors
KeywordsCytokines
Immunoglobulins
Infectious disease
Macrophages
Pulmonology
Issue Date2019
PublisherAmerican Society for Clinical Investigation. The Journal's web site is located at https://insight.jci.org/
Citation
JCI insight, 2019, v. 4 n. 4, p. article no. e123158 How to Cite?
AbstractNewly 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.
Persistent Identifierhttp://hdl.handle.net/10722/272003
ISSN
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorLiu, L-
dc.contributor.authorWei, Q-
dc.contributor.authorLin, Q-
dc.contributor.authorFang, J-
dc.contributor.authorWang, H-
dc.contributor.authorKwok, H-
dc.contributor.authorTang, H-
dc.contributor.authorNishiura, K-
dc.contributor.authorPeng, J-
dc.contributor.authorWu, Z-
dc.contributor.authorWu, T-
dc.contributor.authorCheung, KW-
dc.contributor.authorChan, KH-
dc.contributor.authorAlvarez, X-
dc.contributor.authorQin, C-
dc.contributor.authorLackner, A-
dc.contributor.authorPerlman, S-
dc.contributor.authorYuen, KY-
dc.contributor.authorChen, Z-
dc.date.accessioned2019-07-20T10:33:48Z-
dc.date.available2019-07-20T10:33:48Z-
dc.date.issued2019-
dc.identifier.citationJCI insight, 2019, v. 4 n. 4, p. article no. e123158-
dc.identifier.issn2379-3708-
dc.identifier.urihttp://hdl.handle.net/10722/272003-
dc.description.abstractNewly 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.-
dc.languageeng-
dc.publisherAmerican Society for Clinical Investigation. The Journal's web site is located at https://insight.jci.org/-
dc.relation.ispartofJCI insight-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectCytokines-
dc.subjectImmunoglobulins-
dc.subjectInfectious disease-
dc.subjectMacrophages-
dc.subjectPulmonology-
dc.titleAnti–spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection-
dc.typeArticle-
dc.identifier.emailLiu, L: liuli71@hkucc.hku.hk-
dc.identifier.emailKwok, H: hauyeek@hku.hk-
dc.identifier.emailChan, KH: chankh2@hkucc.hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.emailChen, Z: zchenai@hku.hk-
dc.identifier.authorityLiu, L=rp00268-
dc.identifier.authorityChan, KH=rp01921-
dc.identifier.authorityYuen, KY=rp00366-
dc.identifier.authorityChen, Z=rp00243-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1172/jci.insight.123158-
dc.identifier.pmid30830861-
dc.identifier.pmcidPMC6478436-
dc.identifier.scopuseid_2-s2.0-85062393219-
dc.identifier.hkuros298506-
dc.identifier.volume4-
dc.identifier.issue4-
dc.identifier.spagee123158-
dc.identifier.epagee123158-
dc.publisher.placeUnited States-

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