一个压力传感器,IRE1α,是需要在组织居民巨细胞的细菌外毒素诱导的介质蛋白-1β的生产
Izumi Sasaki1, Yuri Fukuda-Ohta2, Chihiro Nakai1
1Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan.
Cell reports
|March 23, 2024
概括
霍乱毒素B子单元 (CTB) 通过内细胞网膜应激激活巨细胞中的炎症体. 需要伊诺西的酶1α (IRE1α) 对于这种霍乱毒素诱导的互白素-1β产生至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 微生物学 微生物学
背景情况:
- 霍乱毒素 (CT) 作为一种免疫辅助剂,其B亚单元 (CTB) 诱导巨细胞中介白素-1β (IL-1β) 的产生.
- CTB诱导的IL-1β产生涉及pyrin和NLRP3炎症体,但激活机制尚不清楚.
- 细胞内膜网膜 (ER) 的压力与炎症反应有关.
研究的目的:
- 阐明需要伊诺西的酶1α (IRE1α) 在CT和CTB诱导的炎症酶激活和居住腹膜巨细胞 (RPMs) 中IL-1β产生中的作用.
- 调查CTB触发ER压力和随后的炎症信号的机制.
主要方法:
- 从野生类型和IRE1α缺乏的小鼠中利用了居住性腹膜巨细胞 (RPM).
- 将CT和CTB用于RPM,评估IL-1β的产生.
- 研究了ER应激反应和GM1化物的参与CTB吸收和信号传递.
主要成果:
- CTB被纳入了RPM的ER,诱导了依赖GM1的ER应激反应.
- 缺乏IRE1α的RPM显示CT和CTB诱导的IL-1β产生显著受损.
- 在巨细胞中,CTB诱导的NLRP3和pyrin炎症体的激活需要IRE1α.
结论:
- 需要内醇的酶1α (IRE1α) 对于居住腹巨细胞中CT和CTB诱导的IL-1β产生至关重要.
- 在暴露于霍乱毒素期间,IRE1α在NLRP3和pyrin炎症体的激活中起着至关重要的作用.
- 这项研究揭示了一种新的机制,它将ER压力,IRE1α信号和炎症酶激活与细菌毒素相关联.
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