State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.
Zhejiang Mariculture Research Institute, Wenzhou, Zhejiang, 325005, China.
Fish Shellfish Immunol. 2023 Nov;142:109178. doi: 10.1016/j.fsi.2023.109178. Epub 2023 Oct 18.
The enzyme nitric oxide synthase 2 or inducible NOS (NOS2), reactive oxygen species (ROS) and nitric oxide (NO) are important participants in various inflammatory and immune responses. However, the functional significances of the correlations among piscine NOS2, ROS and NO during pathogen infection remain unclear. In teleost, there are two nos2 genes (nos2a and nos2b). It has been previously reported that zebrafish nos2a behaves as a classical inducible NOS, and nos2b exerts some functions similar to mammalian NOS3. In the present study, we reported the functional characterization of zebrafish nos2a during bacterial infection. We found that zebrafish nos2a promoted bacterial proliferation, accompanied by an increased susceptibility to Edwardsiella piscicida infection. The nagative regulation of zebrafish nos2a during E. piscicida infection was characterized by the impaired ROS levels, the induced NO production and the decreased expressions of proinflammatory cytokines, antibacterial genes and oxidant factors. Furthermore, although both inducing ROS and inhibiting NO production significantly inhibited bacterial proliferation, only inhibiting NO production but not inducing ROS significantly increased resistance to E. piscicida infection. More importantly, ROS supplementation and inhibition of NO completely abolished this detrimental consequence mediated by zebrafish nos2a during E. piscicida infection. All together, these results firstly demonstrate that the innate response mediated by zebrafish nos2a in promoting bacterial proliferation is dependent on the lower ROS level and higher NO production. The present study also reveals that inhibition of NO can be effective in the protection against E. piscicida infection.
酶一氧化氮合酶 2 或诱导型 NOS（NOS2）、活性氧（ROS）和一氧化氮（NO）是各种炎症和免疫反应的重要参与者。然而，鱼类 NOS2、ROS 和 NO 之间的相关性在病原体感染中的功能意义尚不清楚。在硬骨鱼中，有两种 nos2 基因（nos2a 和 nos2b）。以前的研究表明，斑马鱼 nos2a 表现为经典的诱导型 NOS，而 nos2b 发挥一些类似于哺乳动物 NOS3 的功能。在本研究中，我们报道了斑马鱼 nos2a 在细菌感染过程中的功能特征。我们发现，斑马鱼 nos2a 促进细菌增殖，同时对爱德华氏菌感染的易感性增加。在爱德华氏菌感染过程中，斑马鱼 nos2a 的负调控特征表现为 ROS 水平降低、NO 产生增加以及促炎细胞因子、抗菌基因和氧化因子表达下调。此外，尽管诱导 ROS 和抑制 NO 产生都显著抑制了细菌增殖，但只有抑制 NO 产生而不诱导 ROS 产生显著增加了对爱德华氏菌感染的抵抗力。更重要的是，ROS 补充和 NO 抑制完全消除了斑马鱼 nos2a 在爱德华氏菌感染过程中介导的这种有害后果。综上所述，这些结果首次表明，斑马鱼 nos2a 介导的促进细菌增殖的先天反应依赖于较低的 ROS 水平和较高的 NO 产生。本研究还表明，抑制 NO 可以有效预防爱德华氏菌感染。
