缺氧诱导因子1-alpha在粘膜菌期间在呼吸道上皮细胞中的多重作用
Povilas Kavaliauskas1, Yiyou Gu2, Naushaba Hasin3,4
1Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Nature communications
|June 20, 2024
概括
缺氧诱导因子1-alpha (HIF1α) 在肺粘膜病变中具有双重作用. 它有助于真菌入侵,但也促进宿主免疫反应,表明治疗向.
科学领域:
- 传染性疾病 传染性疾病
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 肺粘膜菌是一种严重的真菌感染,由吸入的子引起.
- 呼吸道上皮细胞是最初真菌粘附,发芽和入侵的主要地点.
- 在这个过程中缺氧诱导因子1-alpha (HIF1α) 的作用尚未完全理解.
研究的目的:
- 为了研究HIF1α在呼吸道上皮细胞中在Mucorales感染期间的作用.
- 阐明HIF1α在肺粘膜病变期间宿主-病原体相互作用中的双重功能.
主要方法:
- 在体外感染模型使用气道上皮细胞和Rhizopus delemar.
- 对HIF1α蛋白积累和基因表达的分析.
- 转录组分析以确定差异表达的基因.
- 药理上抑制HIF1α在小鼠模型的肺性粘膜病.
主要成果:
- 粘膜菌感染激活了空气道上皮细胞中的HIF1α信号.
- 抑制HIF1α显著减少了真菌对上皮细胞的入侵.
- 抑制HIF1α降低了由感染诱导的促炎基因的表达.
- 在没有降低真菌负载的情况下,药理上抑制HIF1α在小鼠模型中改善了生存率.
结论:
- HIF1α在肺粘真菌菌中起到相反的作用:促进真菌入侵和促进宿主天生的免疫力.
- 向HIF1α可能通过调节宿主反应来为肺性粘性菌根症提供治疗策略.
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