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

Clinically, MERS-CoV-infected patients have shown atypical pneumonia with dysregulated inflammatory responses. The spleen is an important peripheral lymphoid organ that is able to produce immune response immediately after viral infection. To test our hypothesis that blockade of the C5a-C5aR interaction may reduce spleen damage, spleen tissue was examined in MERS-CoV-infected hDPP4-transgenic mice with or without treatment with the anti-C5aR Ab. The results showed that a significant number of splenic cells presented necrosis or apoptosis, especially in the white pulp (yellow arrow), while numerous inflammatory cells infiltrated the red pulp (Fig. 5a, c, e) . Interestingly, mice provided the anti-C5aR Ab treatment exhibited less spleen damage with less splenic cell necrosis or apoptosis and increased numbers of macrophages were detected in red pulp (blue arrow) (Fig. 5b, d, f) . However, no MERS-CoV replication or viral antigen expression was observed in the spleens of mice in the treated and untreated groups (data not shown). Collectively, these findings suggest that the damages to the spleen tissue were not caused by MERS-CoV replication in the splenocytes but may result from the dysregulated immune and inflammatory responses caused by MERS-CoV infection in the lungs or other susceptible organs. Importantly, the anti-C5aR Ab treatment could significantly attenuate the spleen damage, suggesting that the dysregulated immune and inflammatory responses are likely closely associated with the complement system of the host.