乙-d-manno-heptoses是跨王国的免疫激动剂
Yue Tang1, Xiaoying Tian2,3, Min Wang1,4
1State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
小分子代谢物如腺二酸盐-糖-β-d-曼诺-肝素 (ADP-肝素) 激活了天生的免疫力. 这项研究揭示了包括CDP和UDP- 肝素在内的多种肝素代谢物是跨王国的强有力的免疫激动剂.
科学领域:
- 免疫学
- 微生物学
- 生物化学
背景情况:
- 细菌代谢物,如ADP- 肝素,是已知的先天免疫激动剂.
- 不同生命形式中核酸二酸生物合成酶 (HBEs) 的分布和功能尚未完全理解.
研究的目的:
- 研究HBEs及其合成的肝素代谢物的流行和功能.
- 将新型肝素代谢物描述为潜在的免疫激动剂.
- 阐明肝糖代谢物在先天免疫中的跨王国作用.
主要方法:
- 生物信息分析以确定HBEs中的保存基因 (STTR5).
- 酶测试以确认ADP,CDP和UDP-肝素的合成.
- 使用人体和小鼠细胞和动物模型进行体外和体内测定,以评估不同肝素代谢物引发的免疫反应.
- 在古生物中产生异质ADP-肝糖.
主要成果:
- 功能性HBEs和保存的STTR5基因在细菌,古生物,真核生物和病毒中广泛存在.
- 被确定为由这些酶合成的新型肝素代谢物.
- 与哺乳动物系统中的ADP- 肝相比,CDP和UDP- 肝引起了显著更强的α- 蛋白激酶1 (ALPK1) 依赖性免疫反应.
- 在古生物中产生的ADP- 肝素保留了其先天的免疫激动活性.
结论:
- 包括ADP,CDP和UDP在内的β-d-曼诺-肝酶是保存的,跨王国病原体相关的分子模式.
- 这些代谢物激活了ALPK1依赖的先天免疫信号级联,突出了保存的免疫识别途径.
- 这些发现扩大了我们对天生的免疫力和微生物与宿主相互作用的理解.
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