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系统性宿主炎症诱导特定阶段的转录基因修饰和疟疾寄生虫的慢成熟

Lianne I M Lansink^1,2,3,4, Oliver P Skinner², Jessica A Engel¹

¹QIMR Berghofer Medical Research Institute , Herston, Brisbane, Queensland, Australia.

|July 14, 2023

概括

由感染或免疫刺激引发的全身宿主炎症,减缓了疟疾寄生虫的成熟. 血变化和改变的寄生虫基因活性表明,炎症限制了红细胞 (RBC) 内的寄生虫生长.

科学领域:

* 疟疾寄生虫生物学
* 主体-病原体相互作用
* 免疫学和宿主反应

背景情况:

* 疟疾寄生虫在红细胞 (RBC) 中的成熟受营养和昼夜节律等宿主因素的影响.
* 宿主炎症反应对疟疾寄生虫发展的影响尚不完全理解.

研究的目的:

* 调查系统性宿主炎症是否影响疟疾寄生虫成熟率.
* 确定炎症可能抑制寄生虫发展的机制.

主要方法:

* 在小鼠中诱导全身炎症,使用脂多糖 (LPS) 或急性菌感染.
* 用条件或感染小鼠的血进行体外寄生虫培养.
* 主体血的新陈代谢分析.
* 单细胞RNA测序 (scRNA-seq) 的寄生虫在生物体内.

主要成果:

* 系统性炎症显著减缓了从一代红细胞到下一代的寄生虫成熟.
*炎症宿主中的血在体外直接抑制了寄生虫的成熟,表明存在抑制因素.
*代谢分析显示了显著的血变化,并确定了候选抑制代谢物.
* scRNA-seq显示在循环中的Plasmodium trofhozoites中转录和转化活动的快速,广泛的损害.

结论:

* 系统性宿主炎症通过改变血成分并直接影响寄生虫基因表达,迅速影响疟疾寄生虫的成熟.
* 血中的候选抑制代谢物可能导致观察到的成熟延迟.
* 这项研究揭示了一种新的机制,其中宿主炎症限制了疟疾寄生虫在血液中的生长.

关键词:

流感病毒 (Plasmodium) 是一种流感病毒.主体炎症宿主炎症主体-寄生虫相互作用疟疾疟疾是一种疾病.代谢生物组的代谢生物组寄生虫的成熟过程单细胞转录组学单细胞转录组学

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