mTOR和HIF-1α介导的有氧糖解作为训练免疫的代谢基础
Shih-Chin Cheng1, Jessica Quintin1, Robert A Cramer2
1Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands.
概括
训练有素的免疫力是一种髓状细胞中的表观遗传重编程形式,通过Akt-mTOR-HIF-1α通路增强葡萄糖代谢. 这种新陈代谢转变增加了葡萄糖分解,形成了训练有素的免疫力抵抗感染的基础.
科学领域:
- 免疫学 免疫学 免疫学
- 代谢途径 代谢途径
- 细胞重新编程的细胞重编程.
背景情况:
- 训练有素免疫包括髓状细胞的表观遗传重编程,提供对二次感染的非特异性保护.
- 训练免疫的代谢基础尚未完全理解.
研究的目的:
- 为了研究训练免疫诱导期间单细胞的代谢变化.
- 为了确定调节这些代谢转变的分子途径.
主要方法:
- 在受过Candida albicansβ-glucan培训的人类单细胞中分析了基因组修饰概况和全基因组转录组.
- 使用Akt,mTOR和HIF-1α抑制剂的抑制研究.
- 在小鼠中评估训练免疫力,这些小鼠患有骨髓细胞特异性HIF-1α缺陷.
主要成果:
- 经过训练的单细胞表现出增加的葡萄糖消耗和乳酸盐产量,这表明葡萄糖分解增强.
- 激活dectin-1-Akt-mTOR-HIF-1α通路驱动了这种新陈代谢重编程.
- 抑制Akt,mTOR或HIF-1α废止训练免疫诱导.
- 甲福明损害了对真菌感染的天生的免疫反应.
- 缺乏HIF-1α的小鼠未能对细菌败血症产生训练有素的免疫力.
结论:
- 通过Akt-mTOR-HIF-1α通路调节的有氧糖解是训练免疫的代谢基础.
- 针对这种代谢途径可以为传染病提供新的治疗策略.
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