A1是由病原体连接体诱导,以限制髓状细胞死亡和NLRP3炎症酶激活
Mary Speir1,2, Hazel Tye1,2, Timothy A Gottschalk1,2
1Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, Australia.
EMBO reports
|October 17, 2023
概括
支持生存的蛋白质A1调节免疫细胞中的编程细胞死亡和炎症. 细菌感染可以诱导A1延迟细胞死亡和炎症反应,影响治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 编程细胞死亡途径对于感染期间的天生的免疫力至关重要.
- 内在的亡有助于清除受感染的细胞,但其在感染和炎症潜力期间的调节不明.
研究的目的:
- 调查BCL-2家族成员A1在细菌感染期间调节免疫细胞中亡和炎症中的作用.
- 确定A1如何控制BAX/BAK效应器的激活以及随后的IL-1β成熟.
主要方法:
- 研究了A1对巨细胞和单细胞后脂聚糖 (LPS) 感应中的BAX/BAK激活的控制.
- 分析了A1的转录和后翻译调节.
- 研究了A1对IL-1β成熟和细胞死亡的作用,这些作用是由Neisseria gonorrhoeae衍生的外膜囊泡 (NOMVs) 在体外和A1缺乏的小鼠中触发的.
主要成果:
- A1充当分子静止剂,调节BAX/BAK依赖的亡以及依赖炎酶和独立的IL-1β成熟.
- 在炎症单细胞中的A1诱导限制了细胞死亡和NOMVs的IL-1β激活.
- 在A1缺乏的小鼠中,在NOMV注射后,IL-1β的产生增加.
结论:
- 细菌可以诱导A1表达,延迟髓状细胞死亡并抑制炎症反应.
- 在细菌感染期间,A1在平衡亡和炎症方面发挥着至关重要的作用.
- 研究结果表明A1调制是针对宿主导的抗微生物治疗的潜在策略.
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