肝素结合性血凝素诱导的巨细胞训练免疫:对抗菌菌防御的影响
Yongqiang Li1, Xiuping Jia2, Jinhua Tang1
1Department of Clinical Laboratory, Air Force Medical Center, Beijing 100142, China.
来自Mycobacterium tuberculosis的肝素结合性血凝素 (HBHA) 在免疫细胞中诱导训练免疫力 (TI). 这种先天的免疫记忆通过在表观遗传和代谢上重新编程细胞来增强对结核病的防御能力.
科学领域:
- 免疫学 免疫学 免疫学
- 传染性疾病 传染性疾病
- 细胞生物学 细胞生物学
背景情况:
- 结核病 (TB) 仍然是一个重大的全球卫生挑战.
- 目前的Bacillus Calmette-Guérin (BCG) 疫苗对成人肺结核的有效性有限.
- 训练免疫 (TI) 提供了一种新的方法来增强对感染的先天免疫记忆.
研究的目的:
- 研究Mycobacterium tuberculosis产生的肝素结合性血凝素 (HBHA) 诱导训练免疫 (TI) 的潜力.
- 检查HBHA诱导的巨细胞和人体免疫细胞中TI的细胞和分子机制.
主要方法:
- 用HBHA来训练小鼠RAW264.7巨细胞,人类THP-1巨细胞和人类外周血液单核细胞 (hPBMCs).
- 在二次刺激后测量了促炎性细胞因子表达 (IL-1β,IL-6,TNF-α).
- 进行了表观遗传特征 (H3K4me1,H3K4me3) 和代谢分析 (乳酸盐生产,糖解酶).
- 在感染BCG的HBHA受过训练的巨细胞中评估了细胞内菌素负荷.
主要成果:
- 经过HBHA训练的巨细胞在二次刺激后显示出增强的促炎性细胞因子产生.
- 在细胞因子基因位点观察到H3K4me1和H3K4me3基因标记的升高.
- 增加的乳酸盐生产和增加的糖解酶表达表明了新陈代谢重编程.
- 经过HBHA训练的巨体显示出对细胞内Mycobacterium结核病的控制得到了改善.
结论:
- 在先天免疫细胞中,HBHA有效诱导功能训练免疫 (TI) 现型.
- TI诱导是由协调的表观遗传修饰和代谢变化介导的.
- 作为研究TI和宿主防御抗菌根感染的工具,HBHA显示出希望.
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