脑膜炎球菌IV型 pili招募极性复合体穿越大脑内皮
Mathieu Coureuil1, Guillain Mikaty, Florence Miller
1Université Paris Descartes, Faculté de Médecine, INSERM (U-570), 75015 Paris, France. mathieu.coureuil@inserm.fr
Science (New York, N.Y.)
|June 13, 2009
概括
脑膜炎菌使用IV型 pili粘附于脑细胞,招募Par3/Par6/PKCzeta复合体. 这会破坏细胞结,使细菌能够突破血脑屏障并引起脑膜炎.
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:
- 第四类 pili 对于细菌病原体粘附于宿主细胞至关重要.
- 脑膜炎菌使用这些 pili 粘附于大脑内皮细胞,促进血脑屏障 (BBB) 的穿越.
- 了解这种相互作用是预防脑膜炎的关键.
研究的目的:
- 为了研究Neisseria meningitidis粘附于人类大脑内皮细胞的分子机制.
- 为了确定在细菌相互作用期间由IV型 pili招募的宿主细胞因子.
- 要阐明这种相互作用如何促进BBB透.
主要方法:
- 与人类大脑内皮细胞共同培养N. meningitidis.
- 免疫光显微镜可视化细菌和宿主蛋白质的局部.
- 宿主细胞极性复合体和细胞间结节蛋白的招募和分布的分析.
主要成果:
- 脑膜炎菌的IV型 pili介导的粘附会将Par3/Par6/PKCzeta极性复合体引入细菌与宿主细胞接口.
- 这种招募会在相互作用部位诱导子宫外细胞间结域.
- 节点蛋白质从细胞细胞边界中耗尽,导致大脑内皮细胞节点的开放.
结论:
- 脑膜炎菌利用宿主细胞极性机制通过IV型皮质来破坏内皮细胞结合.
- 这种机制促进了细菌穿越血脑屏障的转移.
- 针对这种相互作用可以提供针对脑膜炎球菌脑膜炎的新型治疗策略.
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