在Leishmania major感染期间,HIF-α信号调节巨细胞的炎症反应
Lucy G Fry1, Charity L Washam2,3, Hayden Roys1
1Department of Microbiology and Immunology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
Frontiers in immunology
|April 7, 2025
概括
主体炎症,而不是寄生虫,在皮肤莱什曼病中驱动骨髓状HIF-α信号传递. 这种信号影响基因表达和蛋白质翻译,对于理解疾病进展和开发这种被忽视的热带疾病的新疗法至关重要.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 热带医学 热带医学
背景情况:
- 皮肤莱什曼病 (CL) 是一种被忽视的热带疾病,影响全球数百万人.
- 目前的治疗方法往往是无效的,并且没有疫苗存在,这凸显了对新型治疗点的需求.
- 之前的研究将巨细胞HIF-α (低氧诱导因子-α) 与通过淋巴血管生成治疗Leishmania major*感染的伤口愈合有关.
研究的目的:
- 调查巨细胞HIF-α信号在CL中的作用,独立于淋巴血管生成.
- 为了确定寄生虫或宿主炎症是否主要触发骨髓细胞HIF-α信号.
- 阐明在*L.大*感染期间由HIF-α信号诱导的转录组和通路级变化.
主要方法:
- 进行了RNA测序从未完整或删除HIF-α信号的小鼠的巨细胞.
- 巨细胞受到*L.大*感染和/或促炎性刺激.
- 用途分析分析分析了转录组数据,以确定受影响的生物过程.
主要成果:
- *L.大*感染单独诱导了轻微的HIF-α-依赖的转录组变化.
- 联合感染和促炎性刺激诱导了显著的HIF-α依赖和独立的转录基因变化.
- 发现HIF-α在*L.大*感染期间在促炎环境中抑制蛋白质翻译途径.
结论:
- 主体的炎症反应,而不是寄生虫本身,是 *Leishmania* 感染中髓状 HIF-α 信号的主要驱动因素.
- 激活HIF-α会导致一个独特的转录基因程序,特别是在促炎条件下抑制蛋白质翻译.
- 这些发现提供了对宿主-病原体相互作用和对CL的潜在治疗策略的见解.
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