阿斯巴提尔蛋白酶向宿主活性核子复合蛋白,以限制表皮先天免疫力
Sandip Patra1,2, Rupinder Kaur3
1Laboratory of Fungal Pathogenesis, BRIC-Centre for DNA Fingerprinting and Diagnostics, Hyderabad-500039, Telangana, India.
EMBO reports
|September 30, 2024
概括
Candida glabrata yapsins 通过降解 Arpc1B,这是一种对上皮细胞信号传递至关重要的蛋白质,从而阻断免疫细胞的通信. 这会影响中性粒细胞的反应,有助于酵母的生存.
科学领域:
- 微生物学 微生物学
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 表皮-免疫细胞相互作用对于对抗微生物感染至关重要.
- 病原性酵母如Candida glabrata (Cg) 可以逃避宿主防御.
- 了解病原体-宿主信号干扰是开发新疗法的关键.
研究的目的:
- 研究Candida glabrata Yapsins如何干扰宿主上皮细胞的信号传递.
- 为了确定Cg Yapsins. 的特定宿主目标.
- 阐明Cg亚素抑制免疫反应的机制.
主要方法:
- 研究了Cg雅普辛与上皮细胞 (ECs) 之间的相互作用.
- 利用了Cg和宿主蛋白的遗传删除突变 (Arpc1B,p38).
- 分析了蛋白质降解,信号通路 (p38 MAPK) 和细胞因子分泌 (IL-8).
- 在小鼠感染模型中评估免疫细胞透.
主要成果:
- 酸降解了上皮细胞蛋白Arpc1B,这是Arp2/3复合体的一个子单元.
- Arpc1B的降解会破坏actin的组合,并减少ECs的IL-8分泌.
- 降低IL-8会影响中性粒细胞迁移和抗微生物活性,保护Cg.
- Cg雅普辛介导的Arpc1B降解涉及阿基因-142并降低p38 MAPK信号的调节.
- 删除Arpc1B或p38可以提高ECs中的CG存活率.
- 在体内研究表明,Cg Yapsins抑制免疫细胞透和细胞因子释放在感染脏.
结论:
- Cg Yapsins 针对 Arpc1B 破坏了上皮细胞与中性细胞的通信,促进了 Cg 存活.
- Arpc1B是一种新型宿主点,被病原体利用来抑制免疫信号传递.
- 这些发现揭示了将Arpc1B与p38激活和C. glabrata免疫逃避联系在一起的机制.
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