Chen Lan-Lan, Xie Jin, Cao Dong-Dong, Jia Ning, Li Ya-Juan, Sun Hui, Li Wei-Fang, Hu Bing, Chen Yuxing, Zhou Cong-Zhao
Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Science, University of Science and Technology of China, Hefei, Anhui 230027, China; Key Laboratory of Structural Biology, Chinese Academy of Science, Hefei, Anhui 230027, China.
Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Science, University of Science and Technology of China, Hefei, Anhui 230027, China; Chinese Academy of Sciences Key Laboratory of Brain Function and Disease, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
Dev Comp Immunol. 2018 May;82:49-54. doi: 10.1016/j.dci.2018.01.003. Epub 2018 Jan 6.
Following the Aeromonas hydrophila aerolysin, various aerolysin-like pore-forming proteins have been identified from bacteria to vertebrates. We have recently reported the mechanism of receptor recognition and in vitro pore-formation of a zebrafish aerolysin-like protein Dln1/Aep1. However, the physiological function of Aep1 remains unknown. Here we detected that aep1 gene is constitutively expressed in various immune-related tissues of adult zebrafish; and moreover, its expression is significantly up-regulated upon bacterial challenge, indicating its involvement in antimicrobial infection. Pre-injection of recombinant Aep1 into the infected zebrafish greatly accelerated the clearance of bacteria, resulting in significantly increased survival rate. Meanwhile, the induced expression of cytokines such as interleukin IL-1β and tumor necrosis factor TNF-α in zebrafish upon injection of recombinant Aep1 suggested that Aep1 may be a pro-inflammatory protein that triggers the antimicrobial immune responses. However, compared to the overproduction of these cytokines in the infected zebrafish, pre-injection of Aep1 could significantly reduce the expression level of these cytokines, accompanying with a reduced bacterial load. Moreover, the expression profiles through the developmental stages of zebrafish demonstrated that aep1 is activated at the very early stage prior to the maturation of adaptive immune system. Altogether, our findings proved that Aep1 is an innate immune molecule that prevents the bacterial infection.
继嗜水气单胞菌气溶素之后，已从细菌到脊椎动物中鉴定出各种气溶素样成孔蛋白。我们最近报道了斑马鱼气溶素样蛋白Dln1/Aep1的受体识别机制和体外成孔过程。然而，Aep1的生理功能仍然未知。在此，我们检测到aep1基因在成年斑马鱼的各种免疫相关组织中组成性表达；此外，在细菌攻击后其表达显著上调，表明它参与抗菌感染。将重组Aep1预先注射到受感染的斑马鱼中可大大加速细菌的清除，从而显著提高存活率。同时，注射重组Aep1后斑马鱼中白细胞介素IL-1β和肿瘤坏死因子TNF-α等细胞因子的诱导表达表明，Aep1可能是一种触发抗菌免疫反应的促炎蛋白。然而，与受感染斑马鱼中这些细胞因子的过量产生相比，预先注射Aep1可显著降低这些细胞因子的表达水平，并伴有细菌载量的减少。此外，斑马鱼发育阶段的表达谱表明，aep1在适应性免疫系统成熟之前的非常早期就被激活。总之，我们的研究结果证明Aep1是一种预防细菌感染的先天免疫分子。
