粒细胞生成
先天免疫系统
造血
祖细胞
生物
斑马鱼
免疫学
免疫
免疫系统
干细胞
微生物学
细胞生物学
生物化学
基因
作者
Hannah Darroch,Pramuk Keerthisinghe,Yih Jian Sung,Leah Rolland,Anneke Prankerd-Gough,Philip S. Crosier,Jonathan W. Astin,Cathy W. Hall
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:2
标识
DOI:10.1126/sciadv.adf9904
摘要
Hematopoietic stem and progenitor cells (HSPCs) respond to infection by proliferating and generating in-demand neutrophils through a process called emergency granulopoiesis (EG). Recently, infection-induced changes in HSPCs have also been shown to underpin the longevity of trained immunity, where they generate innate immune cells with enhanced responses to subsequent microbial threats. Using larval zebrafish to live image neutrophils and HSPCs, we show that infection-experienced HSPCs generate neutrophils with enhanced bactericidal functions. Transcriptomic analysis of EG neutrophils uncovered a previously unknown function for mitochondrial reactive oxygen species in elevating neutrophil bactericidal activity. We also reveal that driving expression of zebrafish C/EBPβ within infection-naïve HSPCs is sufficient to generate neutrophils with similarly enhanced bactericidal capacity. Our work suggests that this demand-adapted source of neutrophils contributes to trained immunity by providing enhanced protection toward subsequent infections. Manipulating demand-driven granulopoiesis may provide a therapeutic strategy to boost neutrophil function and treat infectious disease.
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