Division of Biological Sciences, Section of Cell and Developmental Biology, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; BCMB Allied Program, Weill Cornell Medical College, New York, NY 10065, USA.
Cell Rep. 2016 Feb 23;14(7):1581-1589. doi: 10.1016/j.celrep.2016.01.055. Epub 2016 Feb 11.
Pathogens attack host cells by deploying toxins that perturb core host processes. Recent findings from the nematode C. elegans and other metazoans indicate that surveillance or "effector-triggered" pathways monitor functioning of these core processes and mount protective responses when they are perturbed. Despite a growing number of examples of surveillance immunity, the signaling components remain poorly defined. Here, we show that CEBP-2, the C. elegans ortholog of mammalian CCAAT-enhancer-binding protein gamma, is a key player in surveillance immunity. We show that CEBP-2 acts together with the bZIP transcription factor ZIP-2 in the protective response to translational block by P. aeruginosa Exotoxin A as well as perturbations of other processes. CEBP-2 serves to limit pathogen burden, promote survival upon P. aeruginosa infection, and also promote survival upon Exotoxin A exposure. These findings may have broad implications for the mechanisms by which animals sense pathogenic attack and mount protective responses.
病原体通过部署扰乱宿主核心进程的毒素来攻击宿主细胞。最近在秀丽隐杆线虫和其他后生动物中的发现表明，监视或“效应子触发”途径监测这些核心过程的功能，并在受到干扰时启动保护反应。尽管监视免疫的例子越来越多，但信号成分仍未得到很好的定义。在这里，我们表明，CEBP-2 是哺乳动物 CCAAT 增强子结合蛋白 γ 的秀丽隐杆线虫同源物，是监视免疫中的关键参与者。我们表明，CEBP-2 与 bZIP 转录因子 ZIP-2 一起作用，在对铜绿假单胞菌外毒素 A 引起的翻译阻断以及其他过程的干扰产生保护反应。CEBP-2 可限制病原体负担，促进铜绿假单胞菌感染后的存活，并促进外毒素 A 暴露后的存活。这些发现可能对动物感知致病攻击和启动保护反应的机制具有广泛的意义。
