Blockade of the C5a–C5aR axis alleviates lung damage in hDPP4-transgenic mice infected with MERS-CoV

Jiang, Yuting; Zhao, Guangyu; Song, Nianping; Li, Pei; Chen, Yuehong; Guo, Yan; Li, Junfeng; Du, Lanying; Jiang, Shibo; Guo, Renfeng; Sun, Shihui; Zhou, Yusen

The histopathology study at day 7 post-infection showed that MERS-CoV infection induced mild to severe interstitial pneumonia with diffused and thickened alveolar septa accompanied by infiltration of lymphocytes, macrophages, and neutrophils, denaturated and collapsed pneumocytes, and multifocal hemorrhage in the interstitial space of lungs (Fig. 4a-c) . Therefore, to elucidate the role of excessive complement activation in infectious MERS-CoV-induced tissue damage, a mAb against the mouse C5a receptor was used to block the interaction of C5a with its receptor C5aR. After treatment, damage was lessened and only mild focal thickened alveolar septa was observed, especially around vessels, and no edema or hemorrhage in lungs was observed (Fig. 4d-f) . A semiquantitative analysis also confirmed the relatively less severe damage of lung tissues (Fig. 4g ). In addition, after blockade, decreased weight loss was observed in the one mouse left alive compared with that observed in the sham treatment group (Fig. 4h, i) , although the single mouse surviving treatment is not significant. The results further indicated that the blockade of the C5a-C5aR axis could alleviate lung damage in hDPP4-transgenic mice, although an antiviral agent inhibiting MERS-CoV infection may be required in combination with the anti-C5aR Ab to increase the survival rate of MERS-CoV-infected mice.