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, lymphopenia occurs in many infectious diseases, such as influenza, HIV, hypotosis, and sepsis. Lymphopenia is also commonly observed in MERS patients. The complement inhibiting, decay-accelerating factor (CD55) has been shown to regulate CD8 + T cell immunity to virus infection 42 . Ward and colleagues 43 and Ward 44 demonstrated that C5aR plays a crucial role in the development of septic lymphopenia and that targeting C5a to prevent lymphopenia can be considered to restore normal immune responses in lieu of "after-the-fact" strategies. Chu et al 45 . demonstrated that MERS-CoV infection induced apoptosis of human primary T lymphocytes involved in the caspase-dependent apoptosis pathway. Our study confirmed that MERS-CoV contributed to apoptosis of splenic cells in vivo, accompanied by severe spleen damage and dysregulated systemic immune response, indicating that T cells play a role in controlling the pathogenesis of MERS-CoV infection. It is possible that regulation of the host immune response by complement improved the status of spleen tissue by decreasing splenic apoptosis and increasing the regeneration of splenic cells, indicating that induction of C5a production by MERS-CoV infection may contribute to the dysregulated immune responses, while blockade of the C5a-C5aR axis may improve outcomes by restoring normal immune responses.