在受感染的巨细胞中,沙门氏菌诱导的胆固醇积累通过mTORC1激活抑制了自
Holly M Torsilieri1,2, Clint M Upchurch3, Norbert Leitinger3
1Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA 22903.
Molecular biology of the cell
|November 27, 2024
概括
沙门氏菌 Typhimurium 感染劫持宿主胆固醇水平以激活mTORC1,抑制自并促进细菌的生存. 防止胆固醇的积累恢复了自,并减少了细菌的数量.
科学领域:
- 微生物学 微生物学
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 沙门氏菌 Typhimurium 感染宿主细胞,颠覆细胞过程.
- 细胞降解途径自被通过mTORC1.1.通过高胆固醇水平抑制.
- 沙门氏菌感染导致胆固醇在巨细胞中积累,其中一些局部化到含沙门氏菌的真空孔 (SCV).
研究的目的:
- 研究胆固醇积累和mTORC1激活在沙门氏菌Typhimurium感染中的作用.
- 阐明沙门氏菌为了生存而操纵宿主脂质稳态的机制.
主要方法:
- 研究了感染巨细胞中SCVs的mTORC1招募和激活.
- 利用药理抑制和基因突变 (sseJ) 来阻止胆固醇的积累.
- 评估了氧结合蛋白1 (OSBP) 在胆固醇转移和mTORC1激活中的作用.
- 对受感染的巨细胞进行了脂质组分析.
主要成果:
- mTORC1以胆固醇依赖的方式被招募到SCV并过度激活.
- 抑制胆固醇积累或seJ突变诱导自和减少细菌存活.
- 氧化醇结合蛋白1 (OSBP) 被招募到SCV中,对于胆固醇转移和mTORC1激活至关重要.
- 沙门氏菌感染会改变巨细胞脂质稳态,有利于细菌的生存.
结论:
- 沙门氏菌Typhimurium利用效应器SseJ来诱导宿主细胞胆固醇的积累.
- 这种胆固醇积累激活mTORC1在SCVs,抑制自和促进细菌的持久性.
- 在调解沙门氏菌诱导的胆固醇转移和mTORC1激活方面,OSBP起着至关重要的作用.
- 准这种途径可能为治疗沙门氏菌感染提供新的策略.
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