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线粒体UPR调节的先天免疫力提供了对病原体感染的抵抗力

Mark W Pellegrino¹, Amrita M Nargund¹, Natalia V Kirienko²

¹Cell Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.

|October 3, 2014

概括

线粒体应激反应因子ATFS-1 (激活转录因子Sestrin-1) 和线粒体展开蛋白反应 (UPRmt) 有助于清除细菌病原体. 增强ATFS-1和UPRmt可以提高病原体清除和生存率.

科学领域:

细胞生物学细胞生物学
免疫学免疫学免疫学
微生物学微生物学

背景情况:

转生动物在肠道等环境中对抗细菌病原体,但机制尚不清楚.
宿主细胞可以利用应激反应来检测病原体并触发天生的免疫力.
由ATFS-1进口效率监控的线粒体功能,调节线粒体未折叠蛋白反应 (UPRmt).

研究的目的:

为了研究ATFS-1在Caenorhabditis elegans中所扮演的角色,研究了对细菌病原体的先天免疫力.
为了确定线粒体应激反应是否有助于病原体的检测和消除.
探索ATFS-1,UPRmt和免疫基因激活之间的联系.

主要方法:

使用Caenorhabditis elegans作为一个模型生物.
暴露于病原体 Pseudomonas aeruginosa 的虫.
监测线粒体功能和ATFS-1进口效率.
评估了ATFS-1和UPRmt对病原体清除和生存的影响.

主要成果:

伪omonas aeruginosa感染诱导了C. elegans中的线粒体功能障碍和UPRmt激活.
缺乏ATFS-1的虫对P. aeruginosa的敏感性增加.
过度激活ATFS-1和UPRmt增强了P. aeruginosa清除和延长生存时间,在很大程度上独立于已知的免疫通路.

结论:

进口效率ATFS-1和UPRmt作为针对线粒体的病原体的监测机制.
这一途径启动了对细菌感染的保护性天生的免疫反应.
准线粒体应激反应可能为抗击感染提供新的策略.

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