虫对2型免疫压力丧失有动态反应
Annabel A Ferguson1, Juan M Inclan-Rico1, Dihong Lu2
1University of Pennsylvania, School of Veterinary Medicine, Pathobiology Department, Philadelphia, Pennsylvania, United States of America.
PLoS pathogens
|December 11, 2023
概括
虫通过改变基因表达来适应宿主免疫力,在免疫缺陷环境中增加生殖产量和大小. 这些变化在再次暴露于正常宿主免疫系统后是可逆的.
科学领域:
- 寄生虫学的寄生虫学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 基因组学就是基因组学.
背景情况:
- 主体免疫对寄生虫转录和健康的影响在很大程度上尚未被探索.
- 众所周知,虫感染会调节宿主免疫力,但反作用尚不清楚.
- 通过信号转换器和转录激活器6 (STAT6) 调节的2型免疫反应对于对成年虫的免疫是至关重要的.
研究的目的:
- 为了研究动物虫Nippostrongylus brasiliensis的适应性变化,当在STAT6缺陷 (STAT6 KO) 的小鼠中连续传递时.
- 分析N. brasiliensis适应STAT6缺乏宿主环境的转录和生理变化.
- 为了确定这些适应在重新引入野生类型 (WT) 主体时的可逆性.
主要方法:
- 在STAT6 KO小鼠中,N. brasiliensis在多代的时间里连续传入.
- 生理学评估包括生殖产量,养能力,能量含量和身体大小.
- 使用改进的N. brasiliensis基因组进行转录分析,以识别基因表达变化.
- 将适应寄生虫重新引入天真的WT宿主,以观察表型和转录恢复.
主要成果:
- 适应STAT6KO宿主的N.brasiliensis表现出增强的生殖产量,养,能量含量和身体尺寸.
- 转录分析显示,卵子生产途径的表达增加,与免疫抑制相关的基因的表达减少 (神经,蛋白酶,SCP/TAPS,跨类蛋白质).
- 在STAT6KO宿主中,免疫抑制基因的下调逐渐发生在多代人中.
- 重新引入WT宿主导致宿主炎症性细胞因子的产生增加,但寄生虫在单次暴露后在形态和转录上与WT适应的虫相似.
结论:
- 尼波斯特朗吉卢斯巴西尼斯 (Nippostrongylus brasiliensis) 具有显著的可塑性,在转录和生理上适应宿主免疫环境.
- 观察到的适应,特别是免疫抑制因素的下调,在暴露于有能力的宿主免疫系统时是可逆的.
- 这种宿主驱动的可塑性可能是寄生性线虫的一般特征,影响宿主-寄生虫相互作用.
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