Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN, USA.
Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN, USA.
J Mol Med (Berl). 2018 Dec;96(12):1293-1306. doi: 10.1007/s00109-018-1710-1. Epub 2018 Nov 1.
Hematopoietic myeloblasts give rise to macrophages, dendritic cells, and neutrophils. Circulating myeloid cells detect invading microbes using pattern recognition receptors and subsequently orchestrate an innate immune response to contain and kill the pathogens. This innate immune response establishes an inflammatory niche characterized by hypoxia due to host and pathogen factors. Hypoxia-inducible factor (HIF) transcription factors are the primary regulators of the myeloid response to hypoxia. In particular, HIF-1α is a critical hub that integrates hypoxic and immunogenic signals during infection or inflammation. Hypoxia induces HIF-1α stabilization, which drives metabolic and phenotypic reprogramming of myeloid cells to maximize antimicrobial potential. HIF-1α activity in myeloid-derived cells enhances the host response to infection, but may also play a role in pathogenic inflammatory processes, such as atherosclerosis. In this review, we summarize recent advances that have elucidated the mechanism by which myeloid cells regulate HIF-1α activity and, in turn, how HIF-1α shapes myeloid cell function.
造血髓样前体细胞可分化为巨噬细胞、树突状细胞和中性粒细胞。循环中的髓样细胞通过模式识别受体来检测入侵的微生物，并随后协调先天免疫反应来限制和杀死病原体。这种先天免疫反应会建立一个炎症微环境，其特点是由于宿主和病原体因素导致的缺氧。缺氧诱导因子 (HIF) 转录因子是髓样细胞对缺氧反应的主要调节因子。特别是，HIF-1α 是在感染或炎症过程中整合缺氧和免疫原性信号的关键枢纽。缺氧诱导 HIF-1α 稳定，从而驱动髓样细胞的代谢和表型重编程，以最大限度地提高抗菌潜力。髓样细胞来源的 HIF-1α 活性增强了宿主对感染的反应，但也可能在动脉粥样硬化等致病炎症过程中发挥作用。在这篇综述中，我们总结了最近的进展，这些进展阐明了髓样细胞调节 HIF-1α 活性的机制，以及 HIF-1α 如何塑造髓样细胞功能。
