Nature：免疫理论新发现

　　

生物通报道，美国迈阿密大学医学院癌症研究中心Hiroki Ishikawa 和Glen N. Barber于10月2号在Nature发表报告，称新发现的STING（Stimulator of Interferon Genes）是启动机体先天免疫系统抵抗细菌或毒感染的分子。

 

先天免疫系统是人类机体抵抗病原感染的重要防御系统。但是，关于先天免疫系统启动的机制至今不清楚，究竟是哪种分子激活免疫系统抵抗DNA病毒或RNA病毒感染，人们不得而知。

 

癌症研究中心的研究人员发现一种可激活干扰素表达的基因STING（Stimulator of Interferon Genes）是启动机体先天免疫的分子 。STING基因最早在干扰素表达筛选的过程中被发现，主要存在与细胞内质网中，据推测含有5个跨膜区域，经由IRF3和NF-κB信号通路促进1型干扰素（IFN- and IFN-）的表达发挥抗病毒的功效。科学家发现，当小鼠STING基因缺失时，小鼠胚胎成纤维细胞对负链病毒的易感性极高，比如说：水泡性口膜炎病毒。

 

STING还与RIG-I蛋白发生相互作用，也与易位子适配蛋白Sec61β发生相互作用，从而说明易位子或在新生多肽向内质网的内部（cisternal 或lumina）空间转位中所涉及的转位通道在先天免疫信号作用中扮演一定角色。

 

Nature原文摘要：STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling

 

【Abstract】

The cellular innate immune system is essential for recognizing pathogen infection and for establishing effective host defence. But critical molecular determinants responsible for facilitating an appropriate immune response—following infection with DNA and RNA viruses, for example—remain to be identified. Here we report the identification, following expression cloning, of a molecule (STING; stimulator of interferon genes) that appears essential for effective innate immune signalling processes. It comprises five putative transmembrane regions, predominantly resides in the endoplasmic reticulum and is able to activate both NF-B and IRF3 transcription pathways to induce expression of type I interferon (IFN- and IFN- ) and exert a potent anti-viral state following expression. In contrast, loss of STING rendered murine embryonic fibroblasts extremely susceptible to negative-stranded virus infection, including vesicular stomatitis virus. Further, STING ablation abrogated the ability of intracellular B-form DNA, as well as members of the herpesvirus family, to induce IFN-, but did not significantly affect the Toll-like receptor (TLR) pathway. Yeast two-hybrid and co-immunoprecipitation studies indicated that STING interacts with RIG-I and with SSR2 (also known as TRAP), which is a member of the translocon-associated protein (TRAP) complex required for protein translocation across the endoplasmic reticulum membrane following translation. Ablation by RNA interference of both TRAP and translocon adaptor SEC61 was subsequently found to inhibit STING's ability to stimulate expression of IFN-. Thus, as well as identifying a regulator of innate immune signalling, our results imply a potential role for the translocon in innate signalling pathways activated by select viruses as well as intracellular DNA.

 

（生物通 张欢）