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 complement system plays an important role in host defense against microbial infection and maintains immune homeostasis. However, complement also contributes to the pathogenesis of many inflammatory and immunological diseases when excessively or inappropriately activated 20 . The biological effector functions of complement are mediated primarily through split products (i.e., C3a and C5a), which promote inflammation via direct and indirect mechanisms upon interaction with their respective receptors, C3a receptor and C5a receptor (C5aR) 21 . In addition to serving as a potent chemoattractant, C5a can also activate leukocytes, stimulate the release of granzymes, and stimulate phagocytosis and respiratory burst of mononuclear cells 22 . Furthermore, C5a induces mononuclear cells to express IL-1 and IL-8 in vitro and enhances IL-6 and TNF-α release in vivo 23 . Antibody (Ab) blockade of C5a or C5aR has been reported to abrogate excessive immune responses in a mouse model of Plasmodium berghei ANKA infection 24 . In our previous studies using H5N1-infected mouse models or an H7N9-infected non-human primate model, inhibition of over-activated complement system alleviated virusinduced acute lung injury 25, 26 .