Innate immunity in teleosts

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蛋白消费量的一半以上，传染病是造成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，未来将继续扩大并支持加拿大的就业。鱼类健康的成本效益比（单位产品相对较低的成本）要求我们确定对传染病的先天抗性标记，以提高存活率，而不严重依赖抗菌剂或昂贵的产品。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（引起细菌性冷水病（BCWD））。VHSV是北美鳟鱼的一种重要的经济疾病，作为一种报告性疾病，一直受到人们的关注。鳃上皮细胞和脾巨噬细胞分别是抵抗VHSV和嗜冷f的关键细胞。分别来自鳃上皮细胞RTgill-W1和脾巨噬细胞RTS11的细胞系提供了有用的模型。鳃上皮的抗菌能力将限制VHSV（或其他病毒）的初始复制，这对减少全身传播和死亡率至关重要。RT脾巨噬细胞吞噬嗜冷f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，循环利用细胞成分。自噬也影响感染因子在细胞内的生长和免疫，对该系统的操纵可以刺激抗病毒和抗菌的耐药性。我们还在RT的实验感染试验中使用传染病剂来确认实验室模型中发现的现象。我们已经发现了一个潜在的非常重要的关于BCWD耐药性的现象，其中RT被喂食一种在商业水产养殖饲料中常见的霉菌毒素，或者鳟鱼被限制饮食，不太容易受到实验感染。这一结果已在基因不同的RT股票中反复证明。了解这一现象对减少水产养殖的生产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对养殖鱼类使用抗菌药物的依赖，并提高生产成本的效率。这笔资金还将培训至多六名研究生和至少十名其他应用和基础水生动物卫生方面的高素质人员，并将使他们在与水产养殖直接相关的职位或其他领域的联合卫生行业就业。

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.