西格拉诱导斑马鱼中性粒细胞的表观遗传重编程
Margarida C Gomes1, Dominik Brokatzky1, Magdalena K Bielecka1
1Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, UK.
Science advances
|September 6, 2023
概括
滋格拉菌感染训练中性粒细胞通过表观遗传变化和线粒体ROS增强细菌清除. 这种训练有素的免疫力为控制脊椎动物的细菌感染提供了潜在的新策略.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 训练有素的免疫包括先天的免疫细胞记忆,增强对再感染的反应.
- 西格拉菌是一种重要的人类病原体,缺乏有效的疫苗.
- 斑马鱼幼虫作为研究先天免疫反应的模型.
研究的目的:
- 为了研究斑马鱼中性粒细胞中Shigella诱导的训练免疫力.
- 阐明这种增强反应背后的表观遗传机制.
- 识别关键的分子参与者,如参与细菌清除的线粒体ROS.
主要方法:
- 斑马鱼幼虫暴露于Shigella以诱导训练免疫力.
- 评估中性粒细胞细菌清除效率.
- 基因组ChIP-seq分析用于映射表观遗传修饰 (H3K4me3).
- 线粒体ROS测量和功能测试.
主要成果:
- 滋格拉培训显著改善斑马鱼中中性粒细胞细菌的清除.
- 滋格拉诱导的保护是非特异性的,不同于BCG或β-葡萄糖训练.
- 表观遗传学分析显示,H3K4me3沉积在1612个基因上,促进微生物的识别和ROS的产生.
- 线粒体ROS对于训练中性粒细胞增强的抗菌活性至关重要.
结论:
- 滋格拉菌感染会在中性粒细胞中诱导强大的训练免疫力,其特征是表观遗传重编程.
- 线粒体ROS是Shigella诱导的增强中性粒细胞抗菌功能的关键调解者.
- 发现的机制为人类的细菌感染提供了潜在的治疗点.
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