在古典激活时,巨细胞经历了核酸代谢的功能性显著重编程
Steven V John1,2, Gretchen L Seim1,3, Billy J Erazo-Flores4,5
1Morgridge Institute for Research, Madison, WI.
bioRxiv : the preprint server for biology
|January 18, 2024
概括
巨细胞在免疫反应期间重编程核酸代谢,从合成转向救援途径. 这种代谢开关对于巨细胞的功能和对病原体的宿主防御至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 代谢途径 代谢途径
- 细胞代谢的细胞代谢.
背景情况:
- 巨细胞代谢对免疫反应至关重要,但主要研究的是中央碳代谢.
- 关于激活巨细胞中核酸代谢重新连接的理解有限.
- 经典的巨细胞激活需要显著的代谢适应.
研究的目的:
- 研究古典巨细胞激活期间核酸代谢的动态变化.
- 阐明调节这些代谢转变的分子机制.
- 确定核酸代谢对巨细胞功能和宿主-病原体相互作用的功能后果.
主要方法:
- 多个omics分析以确定显著改变的代谢途径.
- 同位素追踪研究以追踪代谢流量并确定关键变化.
- 基因操纵 (基因淘汰),以评估特定代谢酶的功能影响.
主要成果:
- 经典的巨细胞激活显著重新连接核酸代谢,关闭 de novo 合成并增加救援通路.
- 氧化 (NO) 在抑制 purin 和 pyrimidine 合成酶 (ATIC,CTPS,TYMS) 中起着关键作用.
- 降解酶 (PNP,UPP) 的上调和NO介导的XOR抑制促进了核酸的挽救.
- 淘汰救援酶素酸转移酶 (Hprt) 损害了巨细胞的功能,促进了寄生虫的生长.
结论:
- 经典激活的巨细胞在核酸代谢中发生了动态转变,优先考虑救援而不是新合成.
- 氧化和转录调节是控制这种代谢重编程的关键机制.
- 核酸代谢的重新连接对于适当的巨细胞功能,宿主防御和控制细胞内寄生虫的增殖至关重要.
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