天生的免疫力.天生的免疫力. 神经生长因子β在脊椎动物对金黄色葡萄球菌的免疫力中扮演着类似斯帕茨尔的角色
Lucy Hepburn1,2, Tomasz K Prajsnar3,4,5, Catherine Klapholz1,2
1Cambridge Institute for Medical Research, University of Cambridge, UK.
概括
神经生长因子β (NGFβ) 在免疫力方面像Spaetzle一样起作用,防止黄金葡萄球菌感染. 这种保存的NGFβ-TRKA信号增强了对细菌病原体的宿主防御机制.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 微生物学 微生物学
背景情况:
- 天生的免疫成分在像虫和人类这样的物种中得到保护.
- 的Toll连接体Spaetzle缺乏已知的脊椎动物对应物.
- 囊结蛋白在宿主防御中的作用在很大程度上是未被探索的.
研究的目的:
- 为了调查潜在的脊椎动物等价物到的托尔连接物Spaetzle.
- 探索神经生长因子β (NGFβ) 在宿主免疫中的作用.
- 阐明NGFβ介导的防治黄金葡萄球菌的机制.
主要方法:
- 对人类NGFβ及其受体TRKA突变的分析,与S. aureus感染的严重程度相关.
- 通过NOD类受体 (NLRP3,NLRP4) 通过S. aureus外蛋白刺激的巨细胞释放NGFβ的研究.
- 评估NGFβ对细胞分裂,杀死细菌,细胞因子产生和中性粒细胞招募的影响.
- 使用带有TrkA倒置的斑马鱼模型来评估金黄色细菌感染的易感性.
主要成果:
- 人类NGFβ或TRKA中的有害突变与严重的金黄色细菌感染相关.
- NGFβ在暴露于S. aureus外蛋白时由巨细胞释放,涉及NLRP3和NLRP4.
- NGFβ增强了巨细胞化和超氧化物依赖的细菌杀死.
- NGFβ刺激促炎性细胞因子的产生和依赖的中性粒细胞的招募.
- 斑马鱼中的TrkA knockdown显著增加了对S. aureus感染的易感性.
结论:
- 神经生长因子β (NGFβ) 在带动物中作为一种类似于Spaetzle的免疫分子起作用.
- NGFβ-TRKA信号传递对于宿主对抗黄金葡萄球菌的防御至关重要.
- 这一途径代表了病原体特异性免疫的进化保守机制.
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