在粘膜屏障的HVEM信号提供了对病原性细菌的宿主防御
Jr-Wen Shui1, Alexandre Larange, Gisen Kim
1Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037, USA.
Nature
|July 18, 2012
概括
疹病毒进入媒介 (HVEM) 对于对抗细菌的先天性粘膜防御至关重要. 用激动剂向HVEM可能会增强肠道和肺部的宿主防御机制.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 细胞生物学 细胞生物学
背景情况:
- 疹病毒进入媒介 (HVEM) 是瘤亡因子受体家族成员,具有多种免疫功能.
- HVEM与大肠炎风险有关,但其在粘膜免疫中的确切作用尚不清楚.
研究的目的:
- 阐明HVEM在对病原性细菌的天生的粘膜防御中的机制.
- 为了研究表皮HVEM在肠道感染期间免疫反应中的作用.
主要方法:
- 使用Citrobacter rodentium感染的小鼠模型来研究Knockout小鼠.
- 分析了受感染小鼠的Stat3激活,基因表达,细菌负担和死亡率.
- 通过免疫学测试确定CD160为表皮HVEM的配体.
主要成果:
- 表皮HVEM通过NF-κB诱导酶依赖的Stat3激活来增强免疫反应.
- 谁−/−小鼠在C. rodentium感染时表现出肠道反应受损,细菌负载增加,死亡率更高.
- CD160被确定为介导宿主保护的表皮HVEM连接体.
- 还发现,HVEM对于宿主抗击Streptococcus pneumoniae肺部感染的防御至关重要.
结论:
- 皮质HVEM通过整合来自先天性淋巴细胞的信号,在先天性粘膜免疫中发挥关键作用.
- 由HVEM诱导的Stat3激活促进了对宿主防御至关重要的上皮基因表达.
- 用激动剂向HVEM是一种潜在的治疗策略,可以增强粘膜免疫力.
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