由饮食氨基酸合成的共生体产生的宿主免疫调节脂质
Sungwhan F Oh1,2, T Praveena3, Heebum Song4
1Department of Immunology, Blavatnik Institute of Harvard Medical School, Boston, MA, USA. soh2@bwh.harvard.edu.
Nature
|November 11, 2021
概括
来自微生物群的分子,如来自Bacteroides fragilis的α-galactosylceramides (BfaGCs) 调节肠道免疫力. 它们的特定分支结构对于激活自然杀伤性T细胞和免疫发育至关重要.
科学领域:
- 免疫学
- 微生物学
- 生物化学
背景情况:
- 共生微生物分子对于肠道免疫成熟至关重要.
- 控制宿主微生物群免疫相互作用的分子机制尚不清楚.
研究的目的:
- 调查来自Bacteroides fragilis的α-银糖胺 (BfaGCs) 的结构特异性免疫调节活性.
- 阐明BfaGCs在调节自然杀手T细胞反应中的分子机制.
主要方法:
- 有针对性的脂质组分析和合成方法.
- 使用一种缺乏分支链氨基酸代谢的 Bacteroides fragilis 淘汰菌株.
- 进行了CD1d-BfaGC-NKT细胞受体复合物的共晶结构和亲和度分析.
主要成果:
- 具有分支链氨基酸代谢受损的B. fragilis产生了分支减少的BfaGC.
- 用突变菌株殖民的小鼠显示结肠NKT细胞调节受损.
- BfaGCs的链分支关键决定了NKT细胞的激活和下游免疫基因表达.
结论:
- BfaGCs作为CD1d受限制的配体,调解免疫调节.
- BfaGCs的结构分支对于它们的免疫调节功能至关重要.
- 这项研究提出了内生代谢物与宿主免疫系统相互作用的分子范式.
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