来自Mycobacterium tuberculosis的硫脂-1激活了Gαq/11结合的通路,以增加感觉神经元的刺激性
Dhananjay K Naik1, Felipe Espinosa1, Ifunanya M Okolie1
1Department of Neuroscience and Center for Advanced Pain Studies, University of Texas at Dallas, Richardson, TX, USA.
Journal of neurophysiology
|December 15, 2025
概括
结核性脂质,特别是硫-1,通过G蛋白合受体直接激活感官神经元,增加神经元刺激能力,并可能导致咳. 这项研究揭示了一种新的机制,将病原体脂质与结核病中的咳反射联系起来.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
背景情况:
- 咳是结核病 (TB) 的主要症状,也是疾病传播的关键因素.
- 之前的研究表明,Mycobacterium tuberculosis脂质提取物 (Mtb提取物) 和其成分硫脂-1 (SL-1) 通过作用于感知神经元可以诱导咳.
- 这种相互作用背后的精确细胞机制尚未完全理解.
研究的目的:
- 阐明Mtb提取物和SL-1调节感知神经元的细胞机制.
- 研究G蛋白结合受体 (GPCRs) 和细胞内信号在Mtb提取物诱导的神经元反应中的作用.
- 为了确定Mtb提取物是否会影响感官神经元的刺激性.
主要方法:
- 成像被用来测量来自小鼠结节和人类背根 (hDRG) 的TRPV1+神经元中的细胞内Ca2+信号.
- 评估了YM254890,Gαq/11抑制剂对Ca2+信号传递的影响.
- 在治疗Mtb提取物后,在小鼠节点性感受体中测量了动作潜能 (AP) 生成和兴奋性.
主要成果:
- Mtb提取物和SL-1在老鼠和人类感官神经元中显著增加了细胞内Ca2+信号.
- 这些Ca2+增加被YM254890减弱,这表明GPCR介导的机制涉及Gαq/11向细胞内Ca2+储存器发送信号.
- Mtb提取物增强了小鼠结节神经元中的AP生成和增加了AP半宽,这表明了电压受控离子通道的调制.
- Mtb 提取物对神经元刺激性和AP 半幅度的影响被 YM254890.0 阻止.
结论:
- 结核病原体衍生的脂质,包括SL-1,通过GPCRs直接激活感官神经元.
- 这种激活涉及Gαq/11信号传递,导致细胞内的增加和神经元刺激性的增强.
- 这些发现提供了结核病脂质与感觉神经元活动调节之间的直接联系,为结核病相关咳的机制提供了洞察力.
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