通过PERK介导的抗氧化反应是病原体在的持久性的关键
Kristin L Rosche1, Joanna Hurtado1,2, Elis A Fisk1
1Department of Veterinary Microbiology and Pathology, Washington State University , Pullman, Washington, USA.
mSphere
|September 21, 2023
概括
传播的病原体,如莱姆病细菌,利用细胞应激通路 (PERK) 在中持续存在. 这一途径激活抗氧化反应,帮助病原体的生存和传播.
科学领域:
- 载体传播疾病 载体传播疾病
- -病原体相互作用
- 这是天生的免疫力.
背景情况:
- 免疫力塑造病原体相互作用,但病原体持久性的机制尚不清楚.
- 传播的病原体必须在关节动物载体中殖民和生存.
研究的目的:
- 为了调查Borrelia burgdorferi和Anaplasma phagocytophilum如何在Ixodes中持续存在,尽管有免疫压力.
- 确定使病原体在载体内生存的分子机制.
主要方法:
- 在Ixodes的PERK通路的药理抑制和RNA干扰 (RNAi).
- 在体内RNAi以评估血和变后的病原体负载.
- 分析PERK路径调节的目标,包括Nrf2.
- nrf2的基因沉默和反应性氧/物种的评估.
主要成果:
- 阻断PERK通路显著降低了虫中的Borrelia burgdorferi和Anaplasma phagocytophilum数量.
- 在活体中,PERK的RNAi降低了病原体的殖民和通过变的生存.
- 病原体通过PERK通路诱导Nrf2抗氧化反应.
- 缺少PERK或Nrf2的细胞显示活性氧/物种增加和微生物存活率降低.
结论:
- 传染性微生物激活了Ixodes PERK通路,促进了病原体的持久性.
- 这一途径增强了Nrf2调节的抗氧化环境,这对病原体的生存至关重要.
- 与PERK-Nrf2轴的干扰显著降低了的病原体数量.
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