肠道微生物组通过1型胆酸IFN信号轴限制阿尔法病毒感染和传播
Emma S Winkler1, Swathi Shrihari2, Barry L Hykes3
1Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Cell
|July 16, 2020
概括
肠道微生物组会影响奇孔尼亚病毒 (CHIKV) 感染的严重程度. 恢复特定的肠道细菌或其代谢物增强抗病毒免疫力,减少CHIKV的传播和传播.
科学领域:
- 病毒学
- 免疫学
- 微生物组研究
背景情况:
- 奇孔尼亚病毒 (CHIKV) 是一种新兴的阿尔法病毒,引起广泛的感染.
- 影响CHIKV疾病严重性的因素尚未完全了解.
- 肠道微生物在CHIKV病变中的作用在很大程度上尚未被探索.
研究的目的:
- 研究肠道微生物群对CHIKV感染和疾病结果的影响.
- 阐明微生物组调节抗病毒免疫力的机制.
主要方法:
- 在没有细菌的小鼠和用抗生素治疗的小鼠身上进行了实验.
- 监测了小孔古尼亚病毒 (CHIKV) 感染和传播情况.
- 分析了托尔类受体7 (TLR7) - MyD88信号传递,I型干扰素 (IFN) 生产和IFN刺激的单细胞基因表达.
- 使用Clostridium scindens或脱氧醇酸进行了微生物组复.
主要成果:
- 肠道微生物群的枯竭导致CHIKV感染的增加,并在24小时内传播.
- 改变的微生物组损害了血细胞树突细胞 (pDC) 中的TLR7- MyD88信号,减少了I型IFN的产生.
- 由于IFN刺激的基因表达减少,循环单细胞对CHIKV感染变得宽容.
- 用Clostridium scindens或脱氧醇酸复制恢复了pDC和MyD88依赖的I型IFN反应,限制了CHIKV感染和传播.
结论:
- 共生性肠道细菌在调节抗病毒免疫力方面发挥着至关重要的作用.
- 由肠道细菌影响的胆酸-pDC-IFN信号轴控制CHIKV的病毒性,传播和传播.
- 针对肠道微生物组或其代谢物是管理CHIKV感染的潜在策略.
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