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

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

doi:10.1172/jci.insight.123158

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SARS-CoV infection and monocytes/macrophages infiltration in the lungs of C-IgG– and S-IgG–treated macaques at 2 dpi.

(A) Representative images of SARS-CoV RNA⁺ (TRITC) and AE1/AE3⁺ (FITC) cells in the lungs of infected macaques (white arrows). The upper photo shows a low magnification overview (200×); the bottom photo shows the boxed area in the upper photo. (B) Representative images of viral protein (NP) immunostaining of the lungs and hilar lymph nodes (LN) of 7 infected and 3 uninfected animals (TRITC, white arrows) (original magnification, 200×). (C) Representative images of viral NP and monocytes/macrophages. These sections showed significantly increased IMMs in the lungs of the S-IgG group compared with the C-IgG group (MAC387⁺, CD163⁺, or CD68⁺; blue arrows). Tissue samples are double-immunostained for the SARS-CoV NP (TRITC) and markers for macrophages, including MAC387 (FITC), CD163 (FITC), and CD68 (FITC). Within the panel of representative images for the C-IgG and S-IgG groups, the left panel shows a low magnification overview; the right panel shows the boxed area in the left panel (original magnification, 200×).