BACH1促进了组织亡和Mycobacterium结核病易感性
Eduardo P Amaral1, Sivaranjani Namasivayam2, Artur T L Queiroz3
1Immunobiology Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, MD, USA. eduardo.amaral@nih.gov.
Nature microbiology
|December 8, 2023
概括
这项研究表明,阻断与结核病相关的基因Bach1可以通过抑制细胞死亡途径铁亡来增强宿主对Mycobacterium tuberculosis (Mtb) 感染的抵抗力.
科学领域:
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
- 病变的发生和发病.
背景情况:
- 氧化应激和铁亡与Mycobacterium tuberculosis (Mtb) 致病的发生有关.
- 转录因子Bach1抑制抗氧化基因,其在Mtb感染中的作用尚不清楚.
研究的目的:
- 为了研究Bach1是否调节宿主对Mtb感染的抵抗力.
- 确定Bach1在Mtb诱导的细胞和组织亡中的作用.
主要方法:
- 在活跃肺结核患者中分析BACH1表达.
- 产生和感染MTB的Bach1缺乏的小鼠和巨细胞.
- 测量谷氨水平,Gpx4表达和脂质过氧化.
- 感染小鼠肺部的单细胞RNA测序.
- 评估mtb细菌负载,死亡和生存率.
主要成果:
- BACH1表达与活性肺结核相关.
- 在小鼠中,Bach1的缺失导致谷氨和Gpx4的增加,抑制了脂质过氧化.
- 缺乏Bach1的巨细胞和小鼠对Mtb的抗性增强,细菌负载减少和亡.
- 单细胞RNA-seq揭示了巴赫1缺乏肺中的铁灭抑制途径.
- 在患有类似人类肺病理的小鼠模型中,Bach1枯竭减少了亡并改善了宿主抵抗力.
结论:
- 在Mtb感染中,Bach1是细胞和组织亡的关键调节者.
- 针对Bach1是一个潜在的策略,可以增强宿主对Mtb.的抵抗力.
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