Complement Receptor C5aR1 Inhibition Reduces Pyroptosis in hDPP4-Transgenic Mice Infected with MERS-CoV
Complement Receptor C5aR1 Inhibition Reduces Pyroptosis in hDPP4-Transgenic Mice Infected with MERS-CoV
复制标题
补体受体 C5aR1 抑制可减少感染 MERS-CoV 的 hDPP4 转基因小鼠的焦亡
DOI：
10.3390/v11010039
复制
发表时间：
2019-01-01
期刊：
影响因子：
4.7
通讯作者：
Sun, Shihui
中科院分区：
文献类型：
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作者：
Jiang, Yuting;Li, Junfeng;Sun, Shihui
中东呼吸综合征冠状病毒（MERS-CoV）是一种高致病性病毒，粗死亡率约为35%。在此之前，我们建立了一个人DPP 4转基因（hDPP 4-Tg）小鼠模型，我们研究了补体过度激活诱导的免疫发病机制。在这里，为了更好地理解MERS-CoV的发病机制，我们研究了MERS-CoV感染的THP-1细胞和hDPP 4 Tg小鼠中的焦亡作用。我们发现MERS-CoV感染诱导人巨噬细胞中的细胞凋亡和补体过度活化。感染MERS-CoV的hDPP 4-Tg小鼠在脾脏中过表达caspase-1，并在血清中显示高IL-1水平，表明感染后发生了细胞凋亡。然而，当C5 a-C5 aR 1轴被抗C5 aR 1抗体（Ab）阻断时，caspase-1和IL-1的表达下降。这些数据表明MERS-CoV感染诱导补体过度活化，这可能导致焦亡和炎症。通过抑制C5 aR 1来抑制焦亡和炎症。这些结果将进一步加深我们对MERS-CoV感染的发病机制的理解。
Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic virus with a crude mortality rate of similar to 35%. Previously, we established a human DPP4 transgenic (hDPP4-Tg) mouse model in which we studied complement overactivation-induced immunopathogenesis. Here, to better understand the pathogenesis of MERS-CoV, we studied the role of pyroptosis in THP-1 cells and hDPP4 Tg mice with MERS-CoV infection. We found that MERS-CoV infection induced pyroptosis and over-activation of complement in human macrophages. The hDPP4-Tg mice infected with MERS-CoV overexpressed caspase-1 in the spleen and showed high IL-1 levels in serum, suggesting that pyroptosis occurred after infection. However, when the C5a-C5aR1 axis was blocked by an anti-C5aR1 antibody (Ab), expression of caspase-1 and IL-1 fell. These data indicate that MERS-CoV infection induces overactivation of complement, which may contribute to pyroptosis and inflammation. Pyroptosis and inflammation were suppressed by inhibiting C5aR1. These results will further our understanding of the pathogenesis of MERS-CoV infection.