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

Through comparative studies with SARS-CoV infection, immune-mediated pathogenesis has been proposed as a potential factor for severe outcome in MERS-CoVinfected patients 11, 12 . SARS patients showing hyperimmune activation, including aberrant expression of interferon (IFN)-stimulated genes and cytokine responses, are likely to succumb to SARS-CoV infection, the severity of which correlates with the amount of inflammatory cytokines present in the serum [13] [14] [15] . Clinical data on the pathogenesis of MERS-CoV infections are sparse. Josset et al. 6 reported that MERS-CoV significantly downregulated the expression of genes involved in the antigen presentation pathway, which, in turn, could affect the development of adaptive immune responses. In addition, proinflammatory cytokines, such as interleukin-1β (IL-1β), IL-6, and IL-8, were markedly induced in Calu-3 cells after MERS-CoV infection 16 . Zhou et al. 10 also speculated that cytokine storms could correlate with the severity of illness, since high levels of proinflammatory cytokines and chemokines were observed to be secreted by human macrophages upon MERS-CoV infection. Previously, we observed aberrant immune responses in MERS-CoVinfected hDPP4-Tg mice, such as elevated secretion of the cytokines IFN-γ-induced protein 10 (IP-10), IFN-γ, tumor necrosis factor-α (TNF-α), and IL-17, all of which are closely associated with virally mediated acute lung injury 14, [17] [18] [19] . Nevertheless, the role of MERS-CoVinduced excessive inflammatory responses as a factor contributing to the severity of disease outcome needs to be further studied.