E. fischeriana Root Compound Dpo Activates Antiviral Innate Immunity.

E. fischeriana Root Compound Dpo Activates Antiviral Innate Immunity.
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E. fischeriana 根化合物 Dpo 激活抗病毒先天免疫

DOI:
10.3389/fcimb.2017.00456
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发表时间:
2017
影响因子:
5.7
通讯作者:
You F
You F
中科院分区:
医学2区
文献类型:
--
作者:
Chen J;Du H;Cui S;Liu T;Yang G;Sun H;Tao W;Jiang B;Yu L;You F

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E. fischeriana 长期以来被用作传统中药。最近的研究报道,费氏桉的一些化合物表现出抗菌和免疫增强活性。先天免疫系统对于内部和外部威胁的免疫监视、初始宿主防御反应和免疫调节至关重要。天然药物化合物(包括费氏桉)在先天免疫调节中的作用在很大程度上尚不清楚。在这里,我们证明了 E. fischeriana 化合物 Dpo 参与抗病毒信号传导。全基因组RNA-seq分析表明,病毒感染对ISG的诱导可以与Dpo协同作用。一致的是,Dpo 增强了抗病毒免疫反应,并保护小鼠在病毒感染期间免于死亡。然而,Dpo 无法挽救 STING 缺陷小鼠因 HSV-1 感染而死亡的情况。 Dpo 对 ISG15 的增强作用在 STING、IRF3、IRF7 或 ELF4 缺陷细胞中也受到损害,这表明 Dpo 以 STING/IRF/ELF4 依赖性方式激活先天免疫反应。因此,STING/IRFs/ELF4 轴对于 Dpo 诱导的 ISGs 表达很重要,并且可以被宿主用来抵抗感染。
E. fischeriana has long been used as a traditional Chinese medicine. Recent studies reported that some compounds of E. fischeriana exhibited antimicrobial and immune enhance activity. Innate immune system is essential for the immune surveillance of inner and outer threats, initial host defense responses and immune modulation. The role of natural drug compounds, including E. fischeriana, in innate immune regulation is largely unknown. Here we demonstrated that E. fischeriana compound Dpo is involved in antiviral signaling. The genome wide RNA-seq analysis revealed that the induction of ISGs by viral infection could be synergized by Dpo. Consistently, Dpo enhanced the antiviral immune responses and protected the mice from death during viral infection. Dpo however was not able to rescue STING deficient mice lethality caused by HSV-1 infection. The enhancement of ISG15 by Dpo was also impaired in STING, IRF3, IRF7, or ELF4 deficient cells, demonstrating that Dpo activates innate immune responses in a STING/IRFs/ELF4 dependent way. The STING/IRFs/ELF4 axis is therefore important for Dpo induced ISGs expression, and can be used by host to counteract infection.
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