TY - JOUR AU - Liu, Li AU - Wei, Qiang AU - Lin, Qingqing AU - Fang, Jun AU - Wang, Haibo AU - Kwok, Hauyee AU - Tang, Hangying AU - Nishiura, Kenji AU - Peng, Jie AU - Tan, Zhiwu AU - Wu, Tongjin AU - Cheung, Ka-Wai AU - Chan, Kwok-Hung AU - Alvarez, Xavier AU - Qin, Chuan AU - Lackner, Andrew AU - Perlman, Stanley AU - Yuen, Kwok-Yung AU - Chen, Zhiwei T1 - Anti–spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection PY - 2019/02/21/ AB - 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. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.123158 VL - 4 IS - 4 UR - https://doi.org/10.1172/jci.insight.123158 PB - The American Society for Clinical Investigation ER -