炎症酶路由由登革热病毒非结构蛋白1激活,在登革热病毒感染期间具有保护作用
Marcus P Wong1,2, Evan Y W Juan1, Felix Pahmeier1,2
1Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, California, United States of America.
PLoS pathogens
|April 25, 2024
概括
登革热病毒非结构蛋白1 (NS1) 激活了巨细胞中的炎症体,导致IL-1β释放. 这种炎症途径对致命的登革热病毒感染起着保护作用.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 细胞生物学 细胞生物学
背景情况:
- 登革热病毒 (DENV) 每年导致数百万例感染,严重病例进展迅速.
- DENV非结构蛋白1 (NS1) 通过破坏内皮壁垒,导致严重的登革热.
- 对于DENV NS1与免疫细胞的相互作用及其在病变发生中的作用仍然不完全理解.
研究的目的:
- 研究DENV NS1如何与巨细胞相互作用并影响炎症酶激活.
- 为了确定炎症酶激活对DENV NS1的反应中的作用.
- 为了阐明DENV感染期间的炎症体路径的保护机制.
主要方法:
- 通过DENV NS1.1,激活小鼠和人类巨细胞中的炎症酶.
- 测量IL-1β释放和评估高热致死.
- 对NLRP3,Pyrin,AIM2和CD14的炎症酶通路依赖性的分析14.
- 在caspase-1/11-deficient和NLRP3-deficient小鼠中评估DENV感染易感性.
主要成果:
- 在巨细胞中,DENV NS1触发了炎症酶激活,诱导了卡斯帕-1依赖的IL-1β释放.
- 这种激活独立于NLRP3,Pyrin和AIM2炎症体,但需要CD14.
- DENV NS1诱导的炎症酶激活不会导致热,从而保持巨细胞的活力.
- 缺乏卡斯帕酶-1/11的小鼠对致命的DENV感染的易感性增加,与缺乏NLRP3的小鼠不同.
结论:
- 炎症酶途径作为巨细胞中DENV NS1的关键传感器.
- 炎症酶激活,独立于 pyroptosis,在对抗 DENV 感染中起着保护作用.
- 准卡斯巴-1/11通路可能为治疗严重登革热提供治疗策略.
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