顺序激活的死亡复合体调节热和IL-1β释放,以应对Yersinia对免疫信号的阻断
Ronit Schwartz Wertman1, Christina K Go1, Benedikt S Saller2,3
1Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, USA 19104.
bioRxiv : the preprint server for biology
|September 25, 2023
概括
耶尔西尼亚尼亚是什么意思
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 微生物病原体的产生
背景情况:
- 耶尔西尼亚毒性因子YopJ通过阻断TAK1和IKK激酶来抑制巨细胞免疫信号传递.
- 巨细胞激活了包括caspase-8和caspase-1在内的备份通路,以进行宿主防御.
- 卡斯帕酶-1激活通常需要炎症体,但Yersinia感染绕过了这一点.
研究的目的:
- 为了阐明在Yersinia感染期间独立于炎症体的caspase-1激活机制.
- 调查酶-8在启动酶-1激活中的作用.
- 了解如何对热致死和IL-1β释放进行差异调节.
主要方法:
- 研究了由Yersinia YopJ触发的caspase-1激活.
- 分析了caspase-8催化和自动处理活动的要求.
- 检查了炎症组分 (ASC,NLRs,NLRP3) 和GSDMD的作用.
- 评估了卡斯帕-8缺失对亡 (RIPK3/MLKL) 和IL-1β释放的影响.
主要成果:
- 由Yersinia激活卡斯帕-1需要卡斯帕-8的催化和自动处理活动.
- 卡斯帕酶-1通过一个涉及GSDMD和NLRP3炎症体的前循环来放大自身的激活.
- 虽然酶-1的激活和细胞死亡是不依赖于炎酶的,但IL-1β的释放需要NLRP3.
- 卡斯帕酶-8的激活是快速和多焦点的,先于延迟的正规炎症细胞组合.
- 卡斯巴-8自动处理防止了MLKL介导的亡;它的缺失触发了NLRP3炎症酶激活.
结论:
- 耶尔西尼亚感染会触发独立于炎症体的卡斯帕-8依赖性热灭菌.
- 卡斯巴酶-1增强了热致死和IL-1β释放,后者依赖于NLRP3炎症酶组合.
- 独特的死亡复合体调解热和IL-1β释放,确保宿主防御Yersinia的免疫逃避.
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