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

Although complement was promptly activated after viral infection, to confirm the efficacy of an anti-C5aR Ab treatment compared to a sham treatment control, we measured local and systemic inflammation in mouse lungs at day 3 post-infection. After treatment, macrophage infiltration was decreased in the lung tissues of mice (Fig. 2a, b) . The expression of IFN-γ receptor, which is primarily expressed in inflammatory cells, was also decreased, as detected by immunohistochemistry (Fig. 2c, d) . Furthermore, the concentration of proinflammatory cytokines, such as IL-1β, TNF-α, IFN-γ, and IL-12, decreased, and the levels of chemokines, such as MCP-1, significantly decreased in the anti-C5aR Ab treatment group. No significant difference in the concentrations of IL-6, IL-10, and IP-10 were detected between the treatment and control groups (Fig. 2ae, eb) . Overall, the results suggested that anti-C5aR Ab treatment could decrease both local and systemic inflammation, especially the T-helper type 1 (Th1) immune response induced by MERS-CoV infection, which may also contribute to tissue damage after MERS-CoV infection.