The therapeutic potential of epigenetic manipulation during infectious diseases.

The therapeutic potential of epigenetic manipulation during infectious diseases.
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传染病期间表观遗传操作的治疗潜力。

DOI:
10.1016/j.pharmthera.2016.07.013
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发表时间:
2016-11
影响因子:
13.5
通讯作者:
Dockrell, David H.
Dockrell, David H.
中科院分区:
医学1区
文献类型:
--
作者:
Cole, Joby;Morris, Paul;Dickman, Mark J.;Dockrell, David H.

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表观遗传修饰在感染性疾病的发病机制中发挥着重要作用。它们代表了调节免疫系统中转录谱的关键机制,其有助于转录应答的细胞类型和刺激特异性。最近的数据强调了表观遗传变化如何影响巨噬细胞功能反应和极化,通过巨噬细胞耐受性和训练影响先天免疫系统。在这篇综述中,我们将探讨组蛋白尾部的翻译后修饰如何影响特定传染病的免疫功能。我们将描述这些可能如何影响结果,突出来自急性细菌病原体,脓毒症模型,病毒潜伏期的维持和HIV感染的反应的例子。我们将讨论如何新兴类的药物,开发用于肿瘤学和其他设置,已被应用于传染病的模型和它们的潜力,以调节细菌感染和HIV治疗的免疫反应的关键方面。
Epigenetic modifications are increasingly recognized as playing an important role in the pathogenesis of infectious diseases. They represent a critical mechanism regulating transcriptional profiles in the immune system that contributes to the cell-type and stimulus specificity of the transcriptional response. Recent data highlight how epigenetic changes impact macrophage functional responses and polarization, influencing the innate immune system through macrophage tolerance and training. In this review we will explore how post-translational modifications of histone tails influence immune function to specific infectious diseases. We will describe how these may influence outcome, highlighting examples derived from responses to acute bacterial pathogens, models of sepsis, maintenance of viral latency and HIV infection. We will discuss how emerging classes of pharmacological agents, developed for use in oncology and other settings, have been applied to models of infectious diseases and their potential to modulate key aspects of the immune response to bacterial infection and HIV therapy.
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