结核菌菌Rv2653蛋白质通过增强糖溶解促进炎症反应
Yaman Du1, Rui Zheng2, Hongli Yin3
1Department of Clinical Laboratory, The 3rd Affiliated Hospital of Kunming Medical University (Yunnan Tumor Hospital), China.
Japanese journal of infectious diseases
|July 30, 2023
概括
来自Mycobacterium tuberculosis的Rv2653蛋白质促进糖解并激活NLRP3炎症体,从而释放炎症因素并抑制细菌的生存. 这一发现为新的结核病治疗策略提供了潜力.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 微生物学 微生物学
背景情况:
- 由Mycobacterium tuberculosis (M.tb) 引起的结核病 (TB) 是全球主要的死亡原因.
- M.tb 蛋白质,特别是来自删除区域 (RD) 的蛋白质,可以通过影响宿主炎症反应和新陈代谢来调解病原性.
研究的目的:
- 研究来自RD13的Rv2653蛋白在调节宿主巨细胞功能中的作用.
- 阐明Rv2653影响宿主细胞代谢和免疫激活的分子机制.
主要方法:
- 克隆和净化Rv2653蛋白质.
- 分析Rv2653对THP1细胞中的糖解和糖解酶表达 (HK2,LDHA) 的影响.
- 研究Rv2653对NLRP3炎症酶激活,mTORC1信号和炎症因子释放的影响.
- 评估Rv2653对细胞内Bacillus Calmette-Guerin (BCG) 存活率的影响.
主要成果:
- 在THP1细胞中,Rv2653显著促进了糖解,并上调了hexokinase 2 (HK2) 和乳酸脱酶-A (LDHA).
- Rv2653诱导的糖解有助于NLRP3炎症酶的激活.
- 通过Rv2653激活哺乳动物目标的拉巴胺素复合物1 (mTORC1) 途径对HK2,LDHA和NLRP3的表达至关重要.
- 与HK2或LDHA的干扰抑制了Rv2653诱导的NLRP3炎症酶激活和炎症因子 (IL-1β,IL-6,TNF-α,ROS,NO) 的释放,同时促进BCG存活.
结论:
- Rv2653通过mTORC1激活促进糖解,导致NLRP3炎症酶激活和炎症因子释放.
- 这些机制最终抑制了细胞内BCG的存活,这表明Rv2653诱导的抗M.tb免疫反应.
- Rv2653代表了开发新型抗结核病治疗策略的潜在目标.
关键词:
在HK2HK2LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA LDHA 是 是 是 是 是 是 是 是 是 是 是 是 是 是 是结核病菌菌菌的结核病菌的结核病菌.在NLRP3中,NLRP3是NLRP3中的一个.在Rv265353中使用.
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