Wang Zhensheng, Ye Canxun, Zhai Wenya, Gao Zexia, Wang Huanling, Liu Hong
College of Fisheries, Key Lab of Freshwater Animal Breeding, Ministry of Agriculture and Rural Affair/Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China; Engineering Research Center of Green Development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education, Wuhan 430070, China.
College of Fisheries, Key Lab of Freshwater Animal Breeding, Ministry of Agriculture and Rural Affair/Key Lab of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China; Engineering Research Center of Green Development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education, Wuhan 430070, China.
Int J Biol Macromol. 2025 Jan;284(Pt 1):138072. doi: 10.1016/j.ijbiomac.2024.138072. Epub 2024 Nov 26.
The potential role of interleukin-34 (IL-34), an important cytokine that regulates intestinal function in mammals, is currently being explored in the context of fish intestinal diseases. In this study, we assessed the preventive potential of recombinant Megalobrama amblycephala IL-34 (rMaIL-34) protein in bacterial enteritis. MaIL-34 exhibited conserved structural and evolutionary features with teleost IL-34 and was found to be involved in the intestinal immune response to Aeromonas hydrophila infection. Furthermore, treatment with rMaIL-34 significantly improved the survival rate of M. amblycephala following A. hydrophila infection and alleviated the symptoms of enteritis in these fish. In vivo, rMaIL-34 enhanced goblet cell proliferation and mucus layer tightness, thereby maintaining mucosal integrity following infection. Additionally, rMaIL-34 attenuated the decrease in ZO-1 expression and inhibited the increase in intestinal permeability caused by A. hydrophila, thereby reducing the concentrations of DAO and D-LAC in the plasma. Furthermore, rMaIL-34 suppressed oxidative stress, apoptosis, and inflammatory responses triggered by A. hydrophila, thereby strengthening the immune barrier. At the microbiological level, rMaIL-34 contributed to improved intestinal microbiota distribution and enhanced the functions of intestinal microbiota in terms of energy metabolism, antibiotic biosynthesis, and oxidative phosphorylation. This study reveals, for the first time, the multiple roles of fish IL-34 in resistance to bacterial enteritis and paves the way for the development of rMaIL-34 as an immunotherapy for bacterial enteritis in fish.
白细胞介素-34（IL-34）是一种调节哺乳动物肠道功能的重要细胞因子，目前正在鱼类肠道疾病的背景下进行研究。在本研究中，我们评估了重组团头鲂IL-34（rMaIL-34）蛋白对细菌性肠炎的预防潜力。MaIL-34与硬骨鱼IL-34具有保守的结构和进化特征，并且发现其参与了对嗜水气单胞菌感染的肠道免疫反应。此外，用rMaIL-34处理显著提高了团头鲂在嗜水气单胞菌感染后的存活率，并减轻了这些鱼的肠炎症状。在体内，rMaIL-34增强了杯状细胞增殖和黏液层紧密性，从而在感染后维持黏膜完整性。此外，rMaIL-34减弱了ZO-1表达的下降，并抑制了嗜水气单胞菌引起的肠道通透性增加，从而降低了血浆中DAO和D-LAC的浓度。此外，rMaIL-34抑制了嗜水气单胞菌引发的氧化应激、细胞凋亡和炎症反应，从而加强了免疫屏障。在微生物学水平上，rMaIL-34有助于改善肠道微生物群分布，并在能量代谢、抗生素生物合成和氧化磷酸化方面增强肠道微生物群的功能。本研究首次揭示了鱼类IL-34在抵抗细菌性肠炎中的多种作用，并为开发rMaIL-34作为鱼类细菌性肠炎的免疫疗法铺平了道路。
