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经历过感染的HSPC通过产生具有增强线粒体杀菌活性的中性粒细胞来防止感染

Hannah Darroch¹, Pramuk Keerthisinghe¹, Yih Jian Sung¹

¹Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.

Science advances

|September 6, 2023

概括

经历过感染的造血干细胞和原始细胞 (HSPCs) 产生具有增强杀伤能力的中性粒细胞,有助于训练免疫力. 这一发现可能会通过促进中性粒细胞功能来促进传染病的新疗法.

科学领域:

免疫学免疫学免疫学
细胞生物学细胞生物学
传染性疾病传染性疾病

背景情况:

造血干细胞和原始细胞 (HSPCs) 对于通过紧急颗粒形成 (EG) 在感染期间产生中性粒细胞至关重要.
感染可以诱导HSPCs的长期变化,有助于训练免疫力和对随后的微生物挑战的增强反应.

研究的目的:

研究感染经验丰富的HSPC如何产生具有增强功能的中性粒细胞.
探索 HSPC 和中性粒细胞感染诱导训练免疫的基础机制.
确定潜在的治疗点,以促进感染性疾病中的中性粒细胞功能.

主要方法:

在斑马鱼幼虫中对中性粒细胞和HSPCs的实时成像.
紧急颗粒形成 (EG) 中性粒细胞的转录组分析.
基因操纵以驱动斑马鱼C/EBPβ在HSPC中的表达.

主要成果:

经历过感染的HSPC产生具有优越杀菌能力的中性粒细胞.
线粒体活性氧物种在增强中性粒细胞杀菌活性方面发挥着关键作用.
在原始的HSPC中,pregulating斑马鱼C/EBPβ模仿了经历过感染的中性粒细胞的增强的杀菌功能.

结论:

在HSPC中,需求驱动的颗粒形成有助于通过增强对再感染的保护来培养免疫力.
向颗粒构造是一种潜在的治疗策略,可以改善中性粒细胞的功能,并对抗传染病.

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