[HTML][HTML] Anti–spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection

L Liu, Q Wei, Q Lin, J Fang, H Wang, H Kwok, H Tang… - JCI insight, 2019 - ncbi.nlm.nih.gov
L Liu, Q Wei, Q Lin, J Fang, H Wang, H Kwok, H Tang, K Nishiura, J Peng, Z Tan, T Wu
JCI insight, 2019ncbi.nlm.nih.gov
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 …
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.
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