Abstract：
Shigella flexneri is a human-adapted pathovar of Escherichia coli that can invade the intestinal epithelium, causing inflammation and bacillary dysentery. Although an important human pathogen, the host response to S. flexneri has not been fully described. Zebrafish larvae represent a valuable model for studying human infections in vivo. Here, we use a Shigella-zebrafish infection model to generate mRNA expression profiles of host response to Shigella infection at the whole-animal level. Immune response-related processes dominate the signature of early Shigella infection (6 h post-infection). Consistent with its clearance from the host, the signature of late Shigella infection (24 h post-infection) is significantly changed, and only a small set of immune-related genes remain differentially expressed, including acod1 and gpr84. Using mutant lines generated by ENU, CRISPR mutagenesis and F0 crispants, we show that acod1- and gpr84-deficient larvae are more susceptible to Shigella infection. Together, these results highlight the power of zebrafish to model infection by bacterial pathogens and reveal the mRNA expression of the early (acutely infected) and late (clearing) host response to Shigella infection.
摘要：
福氏志贺氏菌是一种适应人类的大肠杆菌病态，可以侵入肠上皮，引起炎症和细菌性痢疾.虽然是一种重要的人类病原体，宿主对福氏杆菌的反应尚未完全描述。斑马鱼幼虫代表了研究体内人类感染的有价值的模型。在这里，我们使用志贺氏菌-斑马鱼感染模型在整个动物水平上生成宿主对志贺氏菌感染反应的mRNA表达谱。免疫应答相关过程主导早期志贺氏菌感染(感染后6小时)的特征。与主机的许可一致，晚期志贺氏菌感染（感染后24小时）的特征发生了显着变化，只有一小部分免疫相关基因保持差异表达，包括acod1和gpr84。使用由ENU产生的突变系，CRISPR诱变和F0Crispants,我们表明，缺乏acod1和gpr84的幼虫更容易受到志贺氏菌感染。一起,这些结果突出了斑马鱼模拟细菌病原体感染的能力，并揭示了早期（急性感染）和晚期（清除）宿主对志贺氏菌感染反应的mRNA表达。
