College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
Key Laboratory of Sichuan Province for Fishes Conservation and Utilization in the Upper Reaches of the Yangtze River, Neijiang Normal University, Neijiang, Sichuan, China.
J Fish Dis. 2023 Apr;46(4):321-332. doi: 10.1111/jfd.13746. Epub 2023 Jan 16.
Granulomatous diseases caused by Nocardia seriously endanger the health of cultured fish. These bacteria are widely distributed, but prevention and treatment methods are very limited. Chronic granulomatous inflammation is an important pathological feature of Nocardia infection. However, the molecular mechanisms of granuloma formation and chronic inflammation are still unclear. Constructing a granuloma infection model of Nocardia is the key to exploring the pathogenesis of the disease. In this study, we established a granuloma model in the liver of largemouth bass (Micropterus salmoides) and assessed the infection process of Nocardia seriolae at different concentrations by analysing relevant pathological features. By measuring the expression of pro-inflammatory cytokines, transcription factors and a pyroptosis-related protein, we revealed the close relationship between pyroptosis and chronic inflammation of granulomas. We further analysed the immunofluorescence results and the expression of pyroptosis-related protein of macrophage infected by N. seriolae and found that N. seriolae infection induced macrophage pyroptosis in vitro. These results were proved by flow cytometry analysis of infection experiment in vivo. Our results indicated that the pyroptosis effect may be the key to inducing chronic inflammation in the fish liver and further mediating granuloma formation. In this study, we explored the molecular mechanism underlying chronic inflammation of granulomas and developed research ideas for understanding the occurrence and development of granulomatous diseases in fish.
由奴卡氏菌引起的肉芽肿病严重危害养殖鱼类的健康。这些细菌分布广泛，但预防和治疗方法非常有限。慢性肉芽肿性炎症是奴卡氏菌感染的重要病理特征。然而，肉芽肿形成和慢性炎症的分子机制尚不清楚。构建奴卡氏菌肉芽肿感染模型是探索疾病发病机制的关键。本研究在大口黑鲈（Micropterus salmoides）肝脏中建立了肉芽肿模型，并通过分析相关的病理特征，评估了不同浓度的链霉菌感染的过程。通过测量促炎细胞因子、转录因子和细胞焦亡相关蛋白的表达，我们揭示了细胞焦亡与肉芽肿的慢性炎症之间的密切关系。我们进一步分析了被链霉菌感染的巨噬细胞的免疫荧光结果和细胞焦亡相关蛋白的表达，发现链霉菌感染诱导了体外巨噬细胞细胞焦亡。体内感染实验的流式细胞术分析证实了这些结果。我们的结果表明，细胞焦亡效应可能是诱导鱼肝脏慢性炎症和进一步介导肉芽肿形成的关键。本研究探索了肉芽肿慢性炎症的分子机制，为了解鱼类肉芽肿性疾病的发生和发展提供了研究思路。
