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

To determine whether local complement activation was related to lung damage after MERS-CoV infection, we examined complement activation in lung tissue. The results showed that deposition of C5b-9 increased after viral infection (Fig. 1a-d) . The expression of C5aR in lungs was also increased, especially in the bronchus epithelial cells, pneumocytes, and inflammatory cells, as detected by immunohistochemistry staining (Fig. 1e, f) . The relative expression of C5aR at the transcription level also confirmed the increased complement expression in lung tissue at day 3 post-infection (Fig. 1g) . Furthermore, the presence of C5a in sera, as an indicator of complement activation, was detected by enzyme-linked immunosorbent assay. The results showed that after MERS- CoV infection, the C5a concentration increased at days 1 and 7 but decreased at day 3 post-infection (Fig. 1h) . We speculate that MERS-CoV infection could promptly induce activation of both local and systemic complement activity. Subsequently, the virus-infected host may initiate a self-protection mechanism to suppress the overactivated complement response, resulting in the observed decrease in C5a production. However, continued viral replication may eventually overcome the host response, leading to a stronger complement activation and a rebound in C5a production. These findings suggest a close relationship between systemic inflammatory response and local tissue damage.