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STING 感知微生物活力以调节内细胞网膜的压力介导自
Julien Moretti1, Soumit Roy2, Dominique Bozec3
1The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA.
Cell
|October 24, 2017
概括
活体细菌通过循环-二-腺单酸盐发出危险信号,这种活体PAMP会触发细胞内膜网的压力和细胞生存和免疫力的自.
科学领域:
- 免疫学
- 细胞生物学
- 微生物学
背景情况:
- 构成性细胞自主免疫是一种原始的先天性防御,先于干扰素诱导的反应.
- 细胞利用由病原体相关的分子模式 (PAMPs) 触发的干扰素诱导反应.
- 在感染期间启动构成性细胞自主反应的信号以前是未知的.
研究的目的:
- 在感染期间识别触发构成性细胞自主免疫力的信号.
- 阐明微生物活力信号激活先天免疫反应的机制.
- 了解细胞应激反应如何促进宿主防御和生存.
主要方法:
- 研究了微生物活力信号 (vita-PAMPs) 在激活先天免疫力的作用.
- 作为一种特定的vita-PAMP,利用了来自活体格拉姆阳性细菌的循环二氨酸单酸.
- 检查了干扰素基因刺激器 (STING) 和内质网膜 (ER) 压力的参与.
- 评估了雷帕素 (mTOR) 失活和自的机械性点在ER应激反应中的作用.
- 分析了ER-phagy的过程及其对STING局部化和干扰素反应的影响.
主要成果:
- 在活的克拉姆阳性细菌中确定循环二氨酸单酸作为PAMP.
- 已经证明这种vita-PAMP会激活STING,导致内质网膜应激.
- 显示ER压力会使mTOR失活,从而动员自细胞进行ER封存和压力解决.
- 发现Vita-PAMP诱导的ER-phagy解决了ER压力,并防止了细胞死亡.
- 发现ER-phagy通过将ER-resident STING转移到自细胞来调节干扰素反应.
结论:
- 压力介导ER-phagy是一种细胞自主免疫反应,由STING-依赖的特定vita-PAMP的感知激活.
- 天生的受体利用vita-PAMPs来激活多层的平衡机制,促进免疫力和感染后的生存.
- 这一途径突显了细胞应激,自和先天免疫激活之间的关键联系.
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