Details

Autor(en) / Beteiligte

• Liu, Li
• Wei, Qiang
• Lin, Qingqing
• Fang, Jun
• Wang, Haibo
• Kwok, Hauyee
• Tang, Hangying
• Nishiura, Kenji
• Peng, Jie
• Tan, Zhiwu
• Wu, Tongjin
• Cheung, Ka-Wai
• Chan, Kwok-Hung
• Alvarez, Xavier
• Qin, Chuan
• Lackner, Andrew
• Perlman, Stanley
• Yuen, Kwok-Yung
• Chen, Zhiwei

Titel

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

Ist Teil von

• JCI insight, 2019-02, Vol.4 (4)

Ort / Verlag

United States: American Society for Clinical Investigation

Erscheinungsjahr

2019

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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.