对于XBP-1在保护宿主免受C. elegans免疫激活的重要作用
Claire E Richardson1, Tristan Kooistra, Dennis H Kim
1Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Nature
|February 26, 2010
概括
由X盒结合蛋白1 (XBP-1) 介导的展开蛋白质反应 (UPR) 保护线虫Caenorhabditis elegans在天生的免疫激活期间免受宿主防御诱导的ER压力. 这项研究揭示了XBP-1的存在.
科学领域:
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
- 发育生物学 发展生物学
背景情况:
- 展开的蛋白质反应 (UPR) 是一种保存的细胞机制,用于维持内质网膜 (ER) 恒常性.
- IRE1-XBP1通路是UPR的一个关键分支,对分泌细胞分化至关重要,并与免疫有关.
- 在Caenorhabditis elegans中,先天性免疫依赖于PMK-1 p38 MAPK通路的病原体耐药性.
研究的目的:
- 研究X-box结合蛋白1 (XBP-1) 在先天性免疫中的作用及其与UPR在Caenorhabditis elegans发育过程中的联系.
- 阐明PMK-1 MAPK通路,XBP-1-介导的UPR和对微生物病原体的宿主防御之间的相互作用.
主要方法:
- 在Caenorhabditis elegans中利用了xbp-1和PMK-1的功能丧失突变.
- 被Pseudomonas aeruginosa和非致病细菌感染的野生类型和突变虫.
- 评估ER形态,幼虫死亡率和免疫反应激活.
主要成果:
- 激活PMK-1-介导的先天性免疫反应会在C. elegans中诱导XBP-1-依赖的UPR.
- 丢失xbp-1导致ER形态破坏,并在感染病原性P. aeruginosa.后导致幼虫死亡.
- 失去PMK-1-介导的免疫抑制了感染P. aeruginosa的xbp-1突变体中的幼虫死亡率.
- 过度激活PMK-1会导致xbp-1突变的幼虫死亡,即使没有致病细菌.
结论:
- 在C. elegans发育过程中,先天性免疫作为ER压力的生理诱导剂.
- XBP-1在保护宿主免受与生俱来的免疫反应对微生物的有害影响方面发挥着至关重要的作用.
- 在缓解与建立免疫反应相关的细胞应激方面,XBP-1的保护作用是保留的.
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