Lower vertebrate immunostimulation and effects on host-pathogen interactions

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The long term goals of my research program, as well as the shorter term objectives of this proposal are to better understand parasitic and other infections in fish, the evolutionary drivers that impact the host-parasite relationship, cellular effectors in fish that are important in response to parasitic infection from killing to antigen presentation, and developing better ways of tracking/characterizing these mechanisms in ecologically and economically important fish species. Aquaculture in Canada, and globally, continues to expand producing over half of the fish consumed on an annual basis and filling the demand for the increasing need of sustainable protein sources. In particular, salmon farming is a multi-billion dollar a year industry globally, in which costs/losses to a single parasite, Lepeophtheirus salmonis (sea lice), are estimated at close to a billion dollars a year. Building upon prior NSERC Discovery and Engage grants within our research group we have identified sex-biased and virulence factor genes in L. salmonis that have positive evolutionary selection pressure, and through the use of knock-down/out (KD/KO)-technologies like RNAi have confirmed their importance in both drug resistance (i.e. chitin binding and ABC G/H transporter genes) and the host-parasite (HP) interaction (i.e cathepsins, hypodermins), respectively. As the HP interaction is a two-sided relationship, we have also identified innate and adaptive markers important in the host response to L. salmonis and other parasites. Of note, we have observed major changes in particular T cell populations in salmon with reduced lice infections and identified dendritic-like antigen presenting (AP) cell populations in salmon to be responsive to both vaccination and intracellular parasitic infection. Proliferation of these dendritic-like cells is related to effective AP and immune memory against Kudoa thyrsites, an important parasite causing soft-flesh syndrome in numerous species, but most notably cultured Atlantic salmon in British Columbia. Therefore our objectives are to (1) investigate the relationship between virulence factor genes and host immune responses to lice, (2) determine how virulence factor KD/KO lice compete with wild-type lice over multiple generations and whether they have similarities to less virulent wild-lice species, and (3) characterize this new dendritic-like cell population of salmon to determine its origins, function, and importance in anti-parasitic responses, other pathogens, and effective immune memory. This research is important for identifying the genetic links between environment, immunity, and disease in fish. These links should provide information on how to develop more effective vaccines/immunostimulatory interventions and reduce antibiotic use, in the interest of enhancing industry's ability to produce a healthier and more environmentally sustainable fish.