通过STING介导的新陈代谢重编程在黄金菌感染期间驱动脂质过氧化
Rui Yu1, Naiyan Sun1, Shaodong Fu1
1MOE Joint International Research Laboratory of Animal Health and Food Safety, Key Laboratory of Animal Physiology & Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.
天生的免疫受体STING,或干扰基因刺激器,通过促进脂肪酸合成,驱动脂质积累和氧化应激在黄金葡萄球菌感染期间. 抑制STING可以减轻这些代谢变化.
科学领域:
- 免疫学 免疫学 免疫学
- 代谢途径 代谢途径
- 宿主-病原体相互作用
背景情况:
- 代谢支生理功能,脂肪酸代谢对免疫反应至关重要.
- 天生的免疫受体STING (干扰素基因刺激器) 在感染期间调节新陈代谢.
研究的目的:
- 为了调查STING在宿主脂质代谢中的作用,在黄金葡萄球菌感染期间.
- 阐明STING在对病原体的反应中对细胞代谢进行重新编程的机制.
主要方法:
- 在被S. aureus感染的乳腺上皮细胞中激活STING.
- 分析脂质积累,脂质过氧化物生产和谷氨 (GSH) 水平.
- 研究STING与脂肪酸合成酶 (FASN),基-CoA脱酶2 (SCD2) 和长链乙基-CoA合成酶家族成员4 (ACSL4) 之间的相互作用.
- 使用基因切除和药理上抑制STING.
主要成果:
- 感染细胞中的STING激活导致了显著的脂质积累,增加了脂质过氧化物生产和GSH耗尽.
- 对STING的遗传或药理抑制可以逆转这些代谢变化.
- 发现STING与FASN相互作用,促进新的脂肪酸合成,后者由SCD2和ACSL4进一步处理.
- 这一过程产生不和脂肪酸,导致过氧化和细胞损伤.
结论:
- 在S. aureus感染期间,STING激活在重新编程宿主脂质代谢中起着至关重要的作用.
- STING促进脂肪酸合成和随后的氧化应激,影响宿主防御.
- 向STING提供了一个潜在的治疗策略,用于管理传染病中的代谢失调,并开发抗炎治疗方法.
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