细胞毒性细胞通过粒素介导的粒酶传递杀死细胞内细菌
Michael Walch1, Farokh Dotiwala1, Sachin Mulik1
1Cellular and Molecular Medicine Program, Boston Children's Hospital, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Cell
|June 7, 2014
概括
杀手细胞使用花素将花酶输送到细菌中,通过破坏必需蛋白质并产生活性氧物种 (ROS) 来触发细胞死亡. 这揭示了一种新的抗微生物防御机制.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 细胞生物学 细胞生物学
背景情况:
- 杀手性淋巴细胞使用细胞毒性蛋白酶 (称为大酶) 消除受感染的细胞.
- 在这个过程中,细胞内细菌的命运还不太清楚.
- 人类细胞毒性颗粒含有花素,这是一种在动物中没有发现的抗微生物.
研究的目的:
- 调查花素和花酶在杀死细菌中的作用.
- 阐明大酶诱导细菌死亡的机制.
主要方法:
- 研究了通过花素介导的粒酶到细菌中的传递.
- 分析了酶对细菌蛋白质和大肠杆菌中的通路的影响.
- 评估了在存在ROS食尸体和改变了细菌蛋白质的情况下的细菌存活率.
- 在表达粒素的转基因小鼠中评估了细菌清除率.
主要成果:
- 格拉努利辛将粒酶输送到各种细菌菌株中,导致细菌死亡.
- 大酶分裂细菌电子运输链复合物I和氧化应激蛋白,产生ROS.
- 抑制ROS或破坏关键细菌通路会减缓,但不会防止细菌死亡.
- 接受转基因颗粒素治疗的小鼠显示,对Listeria monocytogenes的清除得到了增强.
结论:
- 格拉努利辛促进了通过格兰酶介导的细胞内细菌的杀死.
- 大酶通过多种机制诱导细菌死亡,包括ROS生成和生命通路的破坏.
- 杀手细胞具有对细菌的内在,强大的抗微生物功能.
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