This project will conduct fundamental research to better understand the nature of antigen-presentation in farm-raised fish with the long-term goal of improving vaccines and vaccine delivery systems for the aquaculture industry. This is one of the most active areas of research in mammalian immunology, but our current understanding of antigen-presentation in marine and freshwater fish is rudimentary at best. We hypothesize that fish, like mammals, have highly specialized antigen-presenting cells known as dendritic cells (DCs) that initiate and shape the adaptive immunity response to microbial pathogens. Although preliminary work from our laboratory provides strong evidence that these cells, in fact, exist, additional studies are needed to 1) validate the role of fish DCs in protective immunity against infectious disease agents; 2) understand their response to microbial cell products; and, 3) determine where, anatomically, antigen-presentation takes place. With the ability to culture these cells in vitro, we will address these questions using a variety of cellular and molecular techniques in the important aquaculture species, rainbow trout, challenged with two well known bacterial pathogens that affect aquaculture worldwide, namely, Yersinia ruckeri and Mycobacterium marinum. The results of these studies will be directly applicable to the design of more effective vaccines for the aquaculture industry thereby enhancing food production, farm efficiency and profitability, while at the same time reducing potential release of antibiotics and antimicrobials into the environment, which can be highly problematic to the human population as a whole.