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Fundamental properties of the mammalian innate immune system revealed by multispecies comparison of type I interferon responses
PLOS Biology ( IF 9.8 ) Pub Date : 2017-12-18 , DOI: 10.1371/journal.pbio.2004086
Andrew E. Shaw , Joseph Hughes , Quan Gu , Abdelkader Behdenna , Joshua B. Singer , Tristan Dennis , Richard J. Orton , Mariana Varela , Robert J. Gifford , Sam J. Wilson , Massimo Palmarini

The host innate immune response mediated by type I interferon (IFN) and the resulting up-regulation of hundreds of interferon-stimulated genes (ISGs) provide an immediate barrier to virus infection. Studies of the type I ‘interferome’ have mainly been carried out at a single species level, often lacking the power necessary to understand key evolutionary features of this pathway. Here, using a single experimental platform, we determined the properties of the interferomes of multiple vertebrate species and developed a webserver to mine the dataset. This approach revealed a conserved ‘core’ of 62 ISGs, including genes not previously associated with IFN, underscoring the ancestral functions associated with this antiviral host response. We show that gene expansion contributes to the evolution of the IFN system and that interferomes are shaped by lineage-specific pressures. Consequently, each mammal possesses a unique repertoire of ISGs, including genes common to all mammals and others unique to their specific species or phylogenetic lineages. An analysis of genes commonly down-regulated by IFN suggests that epigenetic regulation of transcription is a fundamental aspect of the IFN response. Our study provides a resource for the scientific community highlighting key paradigms of the type I IFN response.



中文翻译:

I型干扰素反应的多物种比较揭示了哺乳动物先天免疫系统的基本特性

由I型干扰素(IFN)介导的宿主固有免疫反应以及由此产生的数百种干扰素刺激基因(ISG)的上调为病毒感染提供了直接的屏障。I型“干扰素”的研究主要在单一物种水平上进行,通常缺乏了解该途径关键进化特征的能力。在这里,我们使用一个实验平台,确定了多种脊椎动物物种的干扰素的特性,并开发了一个网络服务器来挖掘数据集。这种方法揭示了62个ISG的保守“核心”,包括以前与IFN不相关的基因,强调了与这种抗病毒宿主反应相关的祖先功能。我们表明,基因扩增有助于干扰素系统的进化,而干扰素受谱系特异性压力的影响。因此,每个哺乳动物都具有独特的ISG组成库,包括所有哺乳动物共有的基因以及其他特定物种或系统发生谱系所独有的基因。对通常被IFN下调的基因的分析表明,转录的表观遗传调控是IFN反应的基本方面。我们的研究为科学界提供了一种资源,重点介绍了I型IFN反应的关键范例。对通常被IFN下调的基因的分析表明,转录的表观遗传调控是IFN反应的基本方面。我们的研究为科学界提供了一种资源,重点介绍了I型IFN反应的关键范例。对通常被IFN下调的基因的分析表明,转录的表观遗传调控是IFN反应的基本方面。我们的研究为科学界提供了一种资源,重点介绍了I型IFN反应的关键范例。

更新日期:2017-12-31
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