ENHANCING RESISTANCE TO MASTITIS IN DAIRY CATTLE

Bovine mastitis is the most important infectious disease affecting both the quality and quantity of milk produced in the United States.Mastitis can cause destruction of milk synthesizing tissues, resulting in decreased milk production and altered secretion composition.Dysfunctional inflammatory responses are a major cause of pathology and are characterized by an imbalance of the robust initial response needed for pathogen clearance and the prompt return to immune homeostasis.Acute and uncontrolledEscherichia colimastitis, for example, often results in severe tissue damage and significant milk production losses in early lactation cows. Macrophages determine the character of the inflammatory response and monocyte/macrophages obtained from early lactation cows have exacerbated pro-inflammatory reactions which can contribute to disease pathogenesis. Previous studies by our group showed that the pro-inflammatory phenotype of blood monocytes is correlated to dramatic changes in the relative amounts of plasma omega 6 (n6) and omega 3 (n3) polyunsaturated fatty acids during the physiological transition from late gestation and into the early lactation period.However, the underlying mechanisms of how polyunsaturated fatty acid metabolism can influence inflammatory-based diseases in early lactation dairy cattle has not been explored in depth. In order to fully harness the potential health benefits of n6:n3 polyunsaturated fatty acid supplementation,there is a critical needto identify the amounts and ratio of fatty acid intake required to alter macrophage-derived oxylipid profiles with the capacity to regulate macrophage-driven inflammatory responses in dairy cows. This new information will positively impact the dairy industry by providing for the first time, science-based recommendations for n6 and n3 PUFA ratios that will mitigate inflammatory-based diseases such as mastitis through nutritional interventions.Therefore, thecentral hypothesisis that enhancing the n3 PUFA content in bovine macrophages will increase pro-resolving oxylipid pools and thus reduce exacerbated inflammatory responses associated with disease pathogenesis in transition cows. The hypothesis will be tested with the following specific:Determine the impact of altered macrophage fatty acid content on oxylipid biosynthesis and inflammatory intracellular signaling pathways.Determine how dietaryfatty acid intake can alter coliform-induced macrophage inflammatory responses through altered oxylipid biosynthesis.The immediate goals of this project are to not only identify how oxylipids profiles shift during times of increased susceptibility to disease, but also determine the potential impact that specific oxylipids have on macrophage inflammatory functions. The long-term goal is to improve mastitis prevention strategies and optimize production efficiency in the dairy industry.