对病毒感染的自然抗性的共生微生物群调节
Kailyn L Stefan1, Myoungjoo V Kim2, Akiko Iwasaki3
1Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Cell
|November 19, 2020
概括
在肠道中诱导干扰素-β (IFN-β) 生产的微生物,特别是它们的外膜糖脂. 这种微生物诱导的IFN-β增强了天然的抗病毒免疫力,提供了潜在的治疗策略.
科学领域:
- 免疫学
- 微生物学
- 分子生物学
背景情况:
- 干扰因子 (IFN-I) 对抗病毒免疫和免疫系统平衡至关重要.
- 在同位状态下,IFN-I信号的起源基本上是未知的.
- 人们越来越认识到共生肠道微生物在宿主免疫力中的作用.
研究的目的:
- 在同位状态条件下识别IFN-I信号的来源.
- 阐明共生微生物诱导IFN-β的机制.
- 探索微生物衍生IFN-β诱导剂的治疗潜力.
主要方法:
- 研究了结肠树突细胞 (DC) 在IFN-I反应中的作用.
- 使用来自 Bacteroidetes 类微生物的外膜 (OM) 相关的甘油脂.
- 使用的 Bacteroides fragilis及其与OM相关的多糖体A (PSA).
- 分析了包括TLR4-TRIF在内的信号通路.
- 在体外和体内 (小鼠模型) 对囊泡性口炎病毒 (VSV) 和流感的抗病毒活性进行评估.
主要成果:
- 开始的微生物通过结肠DC诱导IFN-β的产生.
- 来自Bacteroidetes的外膜糖脂,特别是B. fragilis的PSA,通过TLR4-TRIF信号激活IFN-β的表达.
- 纯化的微生物分子表现出依赖IFN-β诱导的抗病毒活性.
- 在小鼠模型中,同期诱导的IFN-β显著调节了对病毒感染的自然抵抗力.
结论:
- 在恒温条件下,肠道开始性微生物是IFN-β的重要来源.
- 微生物OM相关的甘油脂是通过TLR4-TRIF诱导IFN-β的关键因子.
- 发现微生物IFN-β诱导剂为病毒性疾病提供了新的治疗途径.
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