HIF-1α as a central mediator of cellular resistance to intracellular pathogens.

HIF-1α as a central mediator of cellular resistance to intracellular pathogens.
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DOI:
10.1016/j.coi.2019.05.005
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发表时间:
2019-10
影响因子:
7
通讯作者:
Stanley S
Stanley S
中科院分区:
医学2区
文献类型:
--
作者:
Knight M;Stanley S

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低氧诱导转录因子-1α(HIF-1α)最初被认为是细胞对低氧反应的主要调节因子。最近,缺氧诱导因子-1α已经成为免疫细胞功能的关键调节因子,它将细胞代谢的变化与细胞类型特定的转录输出联系在一起。炎症刺激激活巨噬细胞导致代谢程序有氧糖酵解的诱导和HIF-1α的稳定,这两个过程在正反馈循环中相互加强,有助于推动巨噬细胞的激活。这种有氧糖酵解和HIF-1α的激活对于炎性细胞因子的产生,如IL-1β的产生和细胞对感染的内在控制都是重要的。在这里,我们回顾了HIF-1α对控制细菌、真菌和原生动物细胞内病原体的重要性,重点介绍了最近的发现,揭示了HIF-1α在感染过程中被激活的机制,以及HIF-1α如何协调巨噬细胞的抗微生物反应。
Hypoxia-inducible transcription factor-1α (HIF-1α) was originally identified as a master regulator of cellular responses to hypoxia. More recently, HIF-1α has emerged as a critical regulator of immune cell function that couples shifts in cellular metabolism to cell type- specific transcriptional outputs. Activation of macrophages with inflammatory stimuli leads to induction of the metabolic program aerobic glycolysis and to HIF-1α stabilization, which reinforce one another in a positive feedback loop that helps drive macrophage activation. This activation of aerobic glycolysis and HIF-1α is important both for production of inflammatory cytokines, such as IL-1β, and for cell intrinsic control of infection. Here we review the importance of HIF-1α for control of bacterial, fungal, and protozoan intracellular pathogens, highlighting recent findings that reveal mechanisms by which HIF-1α is activated during infection and how HIF-1α coordinates antimicrobial responses of macrophages.
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