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JCI Insight. 2019 Feb 21;4(4). pii: 123158. doi: 10.1172/jci.insight.123158. eCollection 2019 Feb 21.

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

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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.
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.
Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China.
Division of Comparative Pathology, Tulane National Primate Research Center, Covington, Louisiana, USA.
Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA.
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.


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.


Cytokines; Immunoglobulins; Infectious disease; Macrophages; Pulmonology

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