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Nature:衔接蛋白STING在宿主防卫体系中的作用

来源:Nature 2009-10-10 12:13

衔接蛋白STING(它是“Stimulator of INterferon Genes”的首字母缩写,亦称MITA和ERIS)正在成为先天免疫系统对微生物DNA的反应当中的一个重要组成部分。

Ishikawa等人发现,在没有STING时,小鼠对几种DNA 和 RNA病毒感染的敏感度得到增强。由STING调节的干扰素诱导,要求STING将“TANK-结合激酶-1”从内质网向含有内体囊的Sec5重新定位。这项工作说明,STING可能是宿主抵抗单纯疱疹病毒等DNA病原体所必需的。(生物谷Bioon.com)

生物谷推荐原始出处:

Nature 461, 788-792 (8 October 2009) | doi:10.1038/nature08476

STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity

Hiroki Ishikawa1, Zhe Ma1 & Glen N. Barber1

1 Department of Medicine and Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida 33136, USA
Correspondence to: Glen N. Barber1 Correspondence and requests for materials should be addressed to G.N.B.

The innate immune system is critical for the early detection of invading pathogens and for initiating cellular host defence countermeasures, which include the production of type I interferon (IFN)1, 2, 3. However, little is known about how the innate immune system is galvanized to respond to DNA-based microbes. Here we show that STING (stimulator of interferon genes) is critical for the induction of IFN by non-CpG intracellular DNA species produced by various DNA pathogens after infection4. Murine embryonic fibroblasts, as well as antigen presenting cells such as macrophages and dendritic cells (exposed to intracellular B-form DNA, the DNA virus herpes simplex virus 1 (HSV-1) or bacteria Listeria monocytogenes), were found to require STING to initiate effective IFN production. Accordingly, Sting-knockout mice were susceptible to lethal infection after exposure to HSV-1. The importance of STING in facilitating DNA-mediated innate immune responses was further evident because cytotoxic T-cell responses induced by plasmid DNA vaccination were reduced in Sting-deficient animals. In the presence of intracellular DNA, STING relocalized with TANK-binding kinase 1 (TBK1) from the endoplasmic reticulum to perinuclear vesicles containing the exocyst component Sec5 (also known as EXOC2). Collectively, our studies indicate that STING is essential for host defence against DNA pathogens such as HSV-1 and facilitates the adjuvant activity of DNA-based vaccines.

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