H3K4me3
生物
先天免疫系统
志贺氏菌
重编程
斑马鱼
表观遗传学
免疫系统
微生物学
组蛋白
免疫学
细胞生物学
基因
遗传学
发起人
基因表达
大肠杆菌
作者
Margarida Castro Gomes,Dominik Brokatzky,Magdalena K. Bielecka,Fiona C. Wardle,Serge Mostowy
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2023-09-08
卷期号:9 (36)
被引量:4
标识
DOI:10.1126/sciadv.adf9706
摘要
Trained immunity is a long-term memory of innate immune cells, generating an improved response upon reinfection. Shigella is an important human pathogen and inflammatory paradigm for which there is no effective vaccine. Using zebrafish larvae, we demonstrate that after Shigella training, neutrophils are more efficient at bacterial clearance. We observe that Shigella-induced protection is nonspecific and has differences with training by BCG and β-glucan. Analysis of histone ChIP-seq on trained neutrophils revealed that Shigella training deposits the active H3K4me3 mark on promoter regions of 1612 genes, dramatically changing the epigenetic landscape of neutrophils toward enhanced microbial recognition and mitochondrial ROS production. Last, we demonstrate that mitochondrial ROS plays a key role in enhanced antimicrobial activity of trained neutrophils. It is envisioned that signals and mechanisms we discover here can be used in other vertebrates, including humans, to suggest new therapeutic strategies involving neutrophils to control bacterial infection.
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