共生细菌促进I型干扰素信号传递,以维持小鼠的免疫耐受性
Adriana Vasquez Ayala1, Chia-Yun Hsu1, Renee E Oles1
1Department of Pathology, University of California, San Diego, La Jolla, CA, USA.
The Journal of experimental medicine
|December 12, 2023
概括
细菌 Bacteroides fragilis 使用I型干扰素 (IFN) 来促进肠道中的免疫耐受性. 这涉及调节树突细胞和调节性T细胞,这对于维持肠道健康至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 胃肠病学 胃肠病学
背景情况:
- I型干扰素 (IFN) 是免疫反应的关键,主要研究的是病原体清除.
- 在肠道细菌介导的免疫耐受性中,IFN的作用尚不清楚.
研究的目的:
- 调查免疫调节细菌,特别是 Bacteroides fragilis 是否利用 IFN 途径来支持肠道免疫耐受性.
- 阐明B. fragilis影响树突细胞 (DC) 和调控性T细胞 (Tregs) 的机制.
主要方法:
- 研究了IFN信号在B. fragilis诱导的耐受性中的作用,使用IFNAR1缺乏的DC.
- 在B. fragilis暴露时分析了DC中的IL-10和IL-27的产生.
- 研究了IFN驱动IL-27通过IL-27Rα信号传递对调控性T细胞 (Treg) 分化的影响.
- 利用单细胞RNA测序来分析Treg基因表达,以应对肠道炎症期间B. fragilis殖民.
主要成果:
- IFN信号传递对于B. fragilis诱导的免疫耐受性至关重要.
- 当暴露于B. fragilis时,IFNAR1缺乏的DCs显示IL-10和IL-27的产生减少.
- 来自DC的IFN驱动的IL-27对于通过IL-27Rα信号形成Foxp3+Tregs至关重要.
- 在炎症期间,B. fragilis的殖民诱导了肠道Tregs中特定的IFN基因特征.
结论:
- 像B. fragilis这样的共生细菌可以利用正规的抗病毒途径,特别是I型IFN,促进肠道免疫耐受性.
- 这种机制涉及树突细胞的调节和随后的调节性T细胞的分化,突出了强化型I型IFN信号在宿主微生物相互作用中的新作用.
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