Li Tao, Li Zhan, Chen Fanghong, Liu Xiong, Ning Nianzhi, Huang Jie, Wang Hui
State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, People's Republic of China.
J Infect Dis. 2017 Nov 27;216(9):1150-1158. doi: 10.1093/infdis/jix160.
Enterohemorrhagic Escherichia coli (EHEC) or other attaching/effacing pathogen infections often cause host intestinal inflammation and pathology, which is thought to result in part from a host aggressive innate immune response. However, few effectors that play an important role in this pathology change have been reported. In this study, we discovered a previously unknown EHEC effector, Stk (putative serine/threonine kinase), which induces host aggressive inflammatory response during EHEC infection. Interestingly, homologous proteins of Stk are widely distributed in many pathogens. After translocating into the infected host cells, Stk efficiently phosphorylates IκBα and activates the NF-κB pathway. In EHEC-infected mice, Stk increases serum keratinocyte-derived cytokine (KC) levels and hyperactivates the inflammatory response of the colon, intensifying pathological injury of the colon. The virulence of Stk is based on its eukaryotic-like kinase activity. In conclusion, our data suggest that Stk is a new effector that induces the host aggressive inflammatory response during EHEC infection.
肠出血性大肠杆菌（EHEC）或其他黏附/损伤性病原体感染常导致宿主肠道炎症和病变，这被认为部分是由宿主强烈的先天性免疫反应所致。然而，在这种病理变化中起重要作用的效应蛋白鲜有报道。在本研究中，我们发现了一种此前未知的EHEC效应蛋白Stk（假定的丝氨酸/苏氨酸激酶），它在EHEC感染期间诱导宿主强烈的炎症反应。有趣的是，Stk的同源蛋白广泛分布于许多病原体中。进入受感染的宿主细胞后，Stk有效地磷酸化IκBα并激活NF-κB信号通路。在EHEC感染的小鼠中，Stk会增加血清角质形成细胞衍生细胞因子（KC）水平，并过度激活结肠的炎症反应，加剧结肠的病理损伤。Stk的毒力基于其类真核激酶活性。总之，我们的数据表明，Stk是一种在EHEC感染期间诱导宿主强烈炎症反应的新效应蛋白。
