Zhang Yanqiong, Ma Zhe, Wang Ying, Boyer Joshua, Ni Guoxin, Cheng Liang, Su Siyuan, Zhang Zhigang, Zhu Zhichuan, Qian Jiayi, Su Lishan, Zhang Qi, Damania Blossom, Liu Pengda
Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
iScience. 2020 Aug 14;23(9):101463. doi: 10.1016/j.isci.2020.101463. eCollection 2020 Sep 25.
cGAS/STING signaling plays an essential role in sensing cytosolic DNA. cGAS activity is regulated by posttranslational modifications and binding partners. cGAS interactome largely includes mammalian or viral proteins. Whether and how bacterial proteins bind cGAS to modulate innate immunity remain elusive. Here, we found streptavidin, a secreted bacterial protein, selectively bound cGAS to promote DNA-induced cGAS activation and interferon-β production. Mechanistically, streptavidin enhanced DNA binding and cGAS phase separation, therefore facilitating cGAS activation. Using an HSV-1-infected mouse model, we found streptavidin nanoparticles facilitated HSV-1 clearance through improving innate immunity. Considering the clinical usage of streptavidin as an immune stimulant and drug delivery vehicle and its biotechnological usage for biotin-labeled protein purification and detection, our studies not only provide an example for a bacterial protein regulating cGAS activity but also suggest caution needs to be taken when using streptavidin in various applications given to its ability to induce innate immunity.
cGAS/STING信号通路在感知胞质DNA中起关键作用。cGAS的活性受翻译后修饰和结合伴侣的调控。cGAS相互作用组主要包括哺乳动物或病毒蛋白。细菌蛋白是否以及如何结合cGAS以调节先天免疫仍不清楚。在这里，我们发现链霉亲和素，一种分泌型细菌蛋白，选择性地结合cGAS以促进DNA诱导的cGAS激活和干扰素-β的产生。机制上，链霉亲和素增强了DNA结合和cGAS相分离，从而促进了cGAS的激活。使用单纯疱疹病毒1型感染的小鼠模型，我们发现链霉亲和素纳米颗粒通过改善先天免疫促进了单纯疱疹病毒1型的清除。考虑到链霉亲和素作为免疫刺激剂和药物递送载体的临床应用以及其在生物素标记蛋白纯化和检测中的生物技术应用，我们的研究不仅为细菌蛋白调节cGAS活性提供了一个例子，而且鉴于其诱导先天免疫的能力，提示在各种应用中使用链霉亲和素时需要谨慎。
