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.

我的研究计划和当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。水产养殖消耗了全球一半以上的鱼类蛋白质，而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产业，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（单位产品相对较低的成本）要求我们识别抵抗传染病的先天标记，以提高生存率，而无需严重依赖抗菌药物或昂贵的产品。引起虹鳟鱼（RT）疾病和经济影响的两种重要病原体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）的病因）。这种疾病是北美鳟鱼的一种重要的经济疾病，VHSV 作为一种可报告疾病，始终受到关注。鳃上皮和脾巨噬细胞分别是抵抗 VHSV 和 F. psychrophilum 的关键细胞。鳃上皮细胞的 RTgill-W1 细胞系和脾巨噬细胞的 RTS11 细胞系分别提供了有用的模型。鳃上皮的抗菌能力会限制最初的 VHSV（或其他病毒）复制，对于降低全身传播和死亡率至关重要。 RT 脾巨噬细胞吞噬嗜冷杆菌，但在幼鱼或易感鱼中，细菌增殖，导致组织破坏和死亡。自噬是一种进化上高度保守的系统，存在于酵母和人类中，可回收细胞成分。自噬还影响细胞和免疫中感染因子的生长，并且操纵该系统可以刺激抗病毒和抗菌耐药性。我们还在 RT 实验性感染试验中使用传染病因子来确认实验室模型中发现的现象。我们已经发现了关于 BCWD 抗性的一个潜在非常重要的现象，其中 RT 被喂食商业水产养殖饲料中常见的霉菌毒素，或者限制饮食的鳟鱼不太容易受到实验感染。这一结果已在基因不同的 RT 种群中反复得到证实。了解这一现象可能对减少水产养殖的生产损失和死亡率具有重要意义。该研究计划的一个重要好处是减少养殖鱼类对抗菌药物使用的依赖，并提高生产成本的效率。这笔资金还将培训最多六名研究生和至少十名其他应用和基础水生动物健康方面的高素质人才，并将为他们在联合健康行业就业提供理想的条件，无论是在与水产养殖直接相关的职位上还是在其他领域。