黄金葡萄球菌的油酸酸酶会产生激活宿主PPARα的配体
Christopher D Radka1,2, Matthew W Frank2, Tyler S Simmons2
1Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, KY, United States.
Frontiers in cellular and infection microbiology
|April 11, 2024
概括
10-氧八甲酸 (h18:0),一种来自金黄色葡萄球菌的代谢物,激活PPARα通路. 这种信号轴抑制了对S. aureus皮肤感染的先天免疫反应.
科学领域:
- 微生物学 微生物学
- 免疫学 免疫学 免疫学
- 代谢途径 代谢途径
背景情况:
- 腹腔肠道细菌和病原体金黄色葡萄球菌利用油酸酸酶从不和脂肪酸中产生氧化脂肪酸.
- 这些基化脂肪酸被假设能调节免疫反应,但确切的机制尚未完全理解.
- 10-氧十甲酸 (h18:0) 是S. aureus油酸酸酶在皮肤感染部位产生的关键代谢物.
研究的目的:
- 阐明由油酸酸酶衍生的氧脂肪酸,特别是h18:0,影响宿主免疫反应的信号机制.
- 在免疫细胞中识别h18:0的分子标.
- 为了调查S. aureus皮肤感染的背景下,鉴定的信号通路的作用.
主要方法:
- 用h18:0.0治疗RAW 264.7巨细胞和初级小鼠骨髓衍生巨细胞.
- 基因转录与脂质代谢和Peroxisome Proliferator Activated Receptor (PPAR) 激活有关的基因转录的分析.
- 基于细胞的转录记者测定以确定PPAR亚型的选择性.
- 放射性标记实验以追踪巨细胞内[1-14C]h18:0的代谢命运.
- 在野生型和Ppara-/-淘汰赛巨体中评估h18:0代谢.
- 在使用Ppara-/-淘汰赛小鼠的皮肤感染模型中量化S. aureus负担.
主要成果:
- h18:0治疗诱导了脂质代谢基因的转录,并激活了巨细胞中的PPAR信号传递.
- 转录记者测定表明h18:0可以选择性地激活PPARα.
- 巨细胞通过β-氧化降解h18:0,释放缩短的脂肪酸碎片.
- h18:0 Ppara-/-淘汰赛巨细胞的催化作用显著降低.
- 与野生型对照相比,Ppara-/-淘汰赛小鼠在皮肤感染部位的S. aureus殖民量显著增加.
结论:
- 过氧体增殖器激活受体α (PPARα) 是油酸酸酶衍生氧脂肪酸的直接标,如h18:0.0.
- 一个新的信号轴存在,涉及油酸酸和PPARα.
- 这种油性酸酶-PPARα轴在抑制黄金葡萄球菌 (Staphylococcus aureus) 皮肤感染期间的先天免疫反应中起着至关重要的作用.
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