在Mycobacterium结核病感染期间,自和膜修复的动态相互作用
Jacques Augenstreich1, Anna T Phan1, Charles N S Allen1
1Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland United States of America.
PLoS pathogens
|January 2, 2025
概括
自标志物LC3对Mycobacterium tuberculosis (Mtb) 真空的招募在巨细胞中是动态的和可变的. 这一过程不保证细菌清除或膜修复,挑战了自在宿主防御Mtb.中的作用.
科学领域:
- 细胞微生物学 细胞微生物学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 自对于对抗Mycobacterium tuberculosis (Mtb) 的宿主防御至关重要.
- 在含有Mtb的真空体 (MCV) 上,对自的精确调节和动态尚不完全了解.
研究的目的:
- 实时调查LC3B (LC3) 对MCV的动态招募.
- 确定LC3招募是否与MCV成熟和宿主防御机制与Mtb.相关.
主要方法:
- 开发了一种新的工作流程,用于单细胞和单MCV跟踪,使用时差共聚焦显微镜.
- 量化LC3招募,MCV酸化 (LysoTracker) 和与膜损伤标志物 (盖列-3,OSBP1) 的同定位.
- 评估了干扰素-玛预治疗和ATG7敲击对自和MCV动态的影响.
主要成果:
- ~70%的MCV显示过渡性LC3招募,时间有显著的变化.
- LC3阳性MCVs未能酸化,表明缺乏成熟到自细胞体.
- LC3招募和酸化是相互排斥和可逆的事件.
- LC3招募与膜损伤标志物相关,但与膜修复或ATG7依赖的自无关.
- 干扰素-增加了Mtb诱导的细胞死亡,但没有LC3招募或酸化.
结论:
- 将LC3招募到MCV是一个动态,可逆和异质的过程.
- 自似乎不会调解细胞对Mtb的自主防御或人类巨细胞中MCV的直接膜修复.
- 结合LC3招募和酸化的动态,是发体膜损伤和修复过程的潜在标志物.
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