在慢性感染期间,Mycobacterium结核病存在于缺乏溶酶体的单细胞衍生的肺细胞中
Weihao Zheng1, I-Chang Chang1, Jason Limberis1
1Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, California, United States of America.
PLoS pathogens
|May 3, 2024
概括
结核菌 (Mycobacterium tuberculosis,Mtb) 存在于具有低 lysosome 功能的肺细胞中. 用尼洛尼布等药物准溶酶体生物发生可能为结核病提供新的治疗方法.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 微生物学 微生物学
背景情况:
- 结核菌 (Mycobacterium tuberculosis,Mtb) 感染肺部髓状细胞,但对于慢性感染的特定允许细胞和宿主机制尚不清楚.
- 了解这些因素对于开发有效的结核病疗法至关重要.
研究的目的:
- 在慢性感染期间识别Mtb-允许的肺髓状细胞.
- 描述使Mtb持续存在的宿主机制.
- 探索针对宿主细胞通路的治疗策略.
主要方法:
- 流式细胞计量用于识别髓状细胞子集 (CD11clo,CD11chi,AM,中性粒细胞).
- 转录和功能测试以分析溶酶体通路活性.
- 使用Mtb感染模型和尼洛丁尼治疗的体外和体内研究.
主要成果:
- CD11clo单细胞衍生细胞比其他骨髓状细胞在T细胞反应后拥有更多活的Mtb.
- 这些允许细胞表现出低表达的溶酶体通路 (含量,酸化,TFEB活性).
- Mtb ESX-1分泌系统调解单细胞的招募和分化成允许细胞;尼洛丁尼增强巨细胞溶酶体功能和Mtb控制.
结论:
- Mtb利用溶酶体贫困的肺细胞进行持久性.
- 向溶酶体生物发生是一种潜在的结核病宿主导疗法.
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