Innate immunity in teleosts

硬骨鱼的先天免疫

• 批准号: RGPIN-2022-04086
• 负责人: Lumsden, John
• 金额: $ 2.84万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=761924
• 关键词: Innate; immunity; teleosts

My research program and the studies outlined in the present short-term objectives are designed to better understand innate resistance of fish to infectious disease. Aquaculture is responsible for more than half of all fish protein consumed worldwide and infectious disease is an important cause of lost production. Aquaculture is a growth industry for Canada and will continue to expand and support Canadian jobs in the future. The cost-benefit ratio (relatively low cost per unit product) for fish health requires that we identify innate markers for resistance to infectious disease to provide enhanced survival, without heavy reliance on antimicrobials or expensive products. Two important agents that cause disease and economic impact in rainbow trout (RT) are viral hemorrhagic septicemia virus (VHSV) and Flavobacterium psychrophilum, the cause of bacterial coldwater disease (BCWD). This disease is an economically important disease of trout in North America and VHSV, as a reportable disease, is always of concern. The gill epithelium and the splenic macrophage are key cells that provide for resistance from VHSV and F. psychrophilum, respectively. Cell lines from each, RTgill-W1 for the gill epithelium and RTS11 for the splenic macrophage, respectively, provide useful models. The antimicrobial capabilities of the gill epithelium, which would limit initial VHSV (or other viral) replication, are critical to reduce systemic spread and mortality. The RT splenic macrophage phagocytose F. psychrophilum but in young or susceptible fish the bacteria proliferates causing tissue destruction and mortality. Autophagy is an evolutionarily highly conserved system, present in yeast and humans, that recycles cellular consituents. Autophagy also influences the growth of infectious agents in cells and immunity and manipulation of this system can stimulate antiviral and antibacterial resistance. We also use infectious disease agents in experimental infection trials in RT to confirm the phenomena identified in laboratory models. We have identified a potentially very important phenomenon regarding resistance to BCWD, in which RT were fed a mycotoxin commonly found in commercial aquaculture feeds, or trout which were on a restricted diet, were less susceptible to experimental infection. This outcome has been demonstrated repeatedly in genetically different RT stocks. Understanding this phenomenon could have important implications for reducing production losses and mortality in aquaculture. An important benefit of this research program would be reduced reliance on antimicrobial use in farmed fish and improved efficiency in the cost of production. This funding will also train up to six graduate students and at least ten other highly qualified personnel in applied and basic aquatic animal health and will ideally position them for employment in the allied health industry, either in positions directly related to aquaculture or in other fields.

我的研究计划和目前短期目标中概述的研究旨在更好地了解鱼类对传染病的先天抵抗力。水产养殖占全世界鱼类蛋白消费量的一半以上，传染病是产量损失的一个重要原因。水产养殖是加拿大的一个增长型行业，未来将继续扩大和支持加拿大的就业机会。鱼类健康的成本效益比（单位产品成本相对较低）要求我们确定抗传染病的先天标记，以提高生存率，而不严重依赖抗菌剂或昂贵的产品。导致虹鳟鱼（RT）疾病和经济影响的两个重要因素是病毒性出血性败血症病毒（VHSV）和嗜冷黄杆菌，细菌性冷水病（BCWD）的原因。这种疾病是北美鳟鱼的一种重要经济疾病，VHSV作为一种可报告的疾病，一直受到关注。鳃上皮和脾巨噬细胞是抵抗VHSV和F. psychrophilum）。来自每个的细胞系，RTgill-W1用于鳃上皮和RTS 11用于脾巨噬细胞，分别提供了有用的模型。鳃上皮细胞的抗菌能力，这将限制初始VHSV（或其他病毒）的复制，是至关重要的，以减少全身传播和死亡率。RT脾巨噬细胞吞噬F。但在幼鱼或易感鱼中，细菌增殖导致组织破坏和死亡。自噬是一种在进化上高度保守的系统，存在于酵母和人类中，它使细胞成分发生变化。自噬还影响细胞中感染因子的生长，免疫和对该系统的操纵可以刺激抗病毒和抗菌抗性。我们还在RT的实验性感染试验中使用传染病病原体来证实实验室模型中发现的现象。我们已经确定了一个潜在的非常重要的现象，对BCWD的抗性，其中RT被喂食一种常见于商业水产养殖饲料中的真菌毒素，或限制饮食的鳟鱼，对实验感染不太敏感。这一结果已在遗传上不同的RT种群中反复证明。了解这一现象可能对减少水产养殖的产量损失和死亡率具有重要意义。这项研究计划的一个重要好处是减少了对养殖鱼类抗菌剂使用的依赖，提高了生产成本的效率。这笔资金还将培训多达6名研究生和至少10名其他高素质的应用和基础水生动物健康人员，并将理想地定位他们在联合健康行业就业，无论是在直接相关的水产养殖或其他领域的职位。