1. Anti–spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection
- Author
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Stanley Perlman, Zhiwei Chen, Jun Fang, Jie Peng, Qingqing Lin, Zhiwu Tan, Kenji Nishiura, Chuan Qin, Hauyee Kwok, Ka-Wai Cheung, Kwok-Yung Yuen, Kwok-Hung Chan, Tongjin Wu, Andrew A. Lackner, Qiang Wei, Li Liu, Hang Ying Tang, Haibo Wang, and Xavier Alvarez
- Subjects
Male ,0301 basic medicine ,viruses ,Antibodies, Viral ,Severe Acute Respiratory Syndrome ,0302 clinical medicine ,Medicine ,Neutralizing antibody ,Lung ,Aged, 80 and over ,biology ,General Medicine ,Middle Aged ,respiratory system ,medicine.anatomical_structure ,Pulmonology ,Severe acute respiratory syndrome-related coronavirus ,030220 oncology & carcinogenesis ,Spike Glycoprotein, Coronavirus ,Female ,Antibody ,medicine.symptom ,Research Article ,Adult ,medicine.medical_specialty ,Acute Lung Injury ,Vaccinia virus ,Inflammation ,Lung injury ,Cell Line ,Proinflammatory cytokine ,Young Adult ,03 medical and health sciences ,Internal medicine ,Macrophages, Alveolar ,Animals ,Humans ,Aged ,business.industry ,Monocyte ,Immunization, Passive ,Viral Vaccines ,Antibodies, Neutralizing ,Macaca mulatta ,respiratory tract diseases ,Blockade ,Disease Models, Animal ,030104 developmental biology ,Immunoglobulin G ,Immunology ,biology.protein ,business - 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.
- Published
- 2019