Innate immunity in teleosts

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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.