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Septins
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在肠道上皮细胞中抑制轮状病毒感染的Nlrp9b炎症体
Shu Zhu1, Siyuan Ding2,3, Penghua Wang4
1Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Nature
|June 22, 2017
概括
研究人员发现肠道细胞中的Nlrp9b蛋白与轮状病毒作斗争. 这种蛋白质触发细胞死亡以限制病毒的传播,为抗病毒疗法提供了新的点.
科学领域:
- 免疫学
- 病毒学
- 胃肠病学
背景情况:
- 罗塔病毒导致儿童严重腹,导致严重的死亡率.
- 宿主天生的免疫,特别是NOD类受体 (NLR) 炎症体对肠道病毒的感知和限制机制尚不清楚.
- 肠上皮细胞在抗病毒反应中的作用需要进一步研究.
研究的目的:
- 确定和描述参与限制肠道粘膜中的新宿主因素.
- 阐明NLR Nlrp9b在肠上皮细胞中限制轮状病毒复制的机制.
- 在体内研究Nlrp9b介导的炎症酶激活对宿主防御的作用.
主要方法:
- 在肠道上皮细胞中Nlrp9b表达和功能的特征.
- 用Asc和caspase-1研究NLRP9b炎症组合的形成.
- 在缺乏Nlrp9b的小鼠和体内模型中评估轮状病毒复制和宿主敏感性.
主要成果:
- Nlrp9b 通过RNA螺旋酶 Dhx9 特别识别轮状病毒的短双链RNA (dsRNA).
- Nlrp9b形成炎症体复合体,激活IL-18成熟和Gsdmd诱导的热.
- 在小鼠中减少Nlrp9b或炎症组分增加了对轮状病毒感染的敏感性.
结论:
- 在肠道上皮细胞中,Nlrp9b充当了对轮状病毒的先天免疫的关键传感器和效应器.
- 这种Nlrp9b- 炎症酶途径通过热死来限制轮状病毒的复制.
- 这一途径代表了对抗轮状病毒和其他病毒病原体的宿主防御的潜在治疗标.
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