莱姆病螺旋体的超内皮细胞迁移涉及螺旋体内部化作为通过涉及Cdc42和Rac1的跨细胞通路的中间步骤
bioRxiv : the preprint server for biology
|September 24, 2024
概括
伯格多弗里菌通过细胞间路线通过内皮细胞传播,而不是通过交叉结口传播. 这个过程需要宿主蛋白Cdc42进入,Rac1退出.
科学领域:
- 微生物学 微生物学
- 细胞生物学 细胞生物学
- 病变的发生和发病.
背景情况:
- 由Borrelia burgdorferi引起的Lyme borreliosis是北半球最常见的传播疾病.
- B. burgdorferi的血液传播对其病变产生至关重要,但仍然不太了解.
- 了解B. burgdorferi如何穿越内皮细胞是解释其系统传播和各种临床表现的关键.
研究的目的:
- 研究Borrelia burgdorferi在人类微血管内皮细胞中传播的分子机制.
- 为了确定B. burgdorferi. 使用的内皮细胞穿越路线.
- 确定参与B. burgdorferi入侵和随后迁移的宿主细胞蛋白质.
主要方法:
- 利用培养的初级和永生的人类微血管内皮细胞.
- 使用显微镜观察了B. burgdorferi的转移.
- 使用抑制剂阻断内皮结和常见的内细胞通路.
- 使用特定抑制剂研究了宿主蛋白Cdc42和Rac1的作用.
主要成果:
- 大约55%的野生型B. burgdorferi成功穿越了内皮细胞单层.
- 螺旋虫利用了一条跨细胞路线,通过细胞体而不是在结点进入细胞体.
- 抑制Cdc42减少了B. burgdorferi的内部化,而抑制Rac1则损害了细胞的退出.
- 鉴定出Cdc42和Rac1是B. burgdorferi转移的重要宿主蛋白.
结论:
- 博雷利亚burgdorferi采用一个跨细胞途径通过内皮细胞传播.
- 通过Cdc42进行螺旋体内化和随后通过Rac1调解的退出是这个过程中的关键步骤.
- 这项研究确定了Cdc42和Rac1作为第一个宿主蛋白质,与B. burgdorferi在内皮细胞中传播有关.
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