一个细菌效应器在细胞死亡模式中操纵宿主 lysosomal 蛋白酶活动依赖的可塑性,以促进感染
Zhe Lu1,2, Yong Zhang1, Yanzhao Zhong1,2
1Chinese Academy of Sciences (CAS) Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
概括
结核菌菌分泌Mce3C,一种蛋白质,通过抑制甲素B (CTSB) 来操纵宿主细胞死亡途径. 这促进了细菌的生存和结核病的肺病理.
科学领域:
- 微生物学 微生物学
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 病原体利用宿主细胞死亡途径生存.
- 了解病原体如何操纵细胞死亡对于控制感染至关重要.
研究的目的:
- 确定调节宿主细胞死亡模式的致病因素.
- 研究Mycobacterium结核病 (Mtb) 重编程细胞死亡的机制.
主要方法:
- 识别了Mce3C作为分泌的Mtb蛋白.
- 研究了Mce3C与宿主cathepsin B (CTSB) 的相互作用.
- 评估了Mce3C-CTSB相互作用对亡和亡的影响.
主要成果:
- Mce3C抑制了CTSB的活动,防止了亡 (tBID产生) 和促进了亡 (RIPK1丰富).
- 破坏Mce3C-CTSB相互作用会使细胞死亡转向细胞亡,而不是死亡.
- 在小鼠中,抑制Mce3C-CTSB相互作用减弱了Mtb生存率和肺免疫病理学.
结论:
- Mtb利用Mce3C通过CTSB操纵宿主细胞死亡的可塑性.
- 病原体可以重新编程宿主细胞死亡模式,以促进感染和病原性.
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