Mechanisms and Genes that Shape Bovine Host Defence and Impact Disease Outcomes in High and Low Immune Responder Phenotypes

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This research addresses genetic and epigenetic mechanisms that control bovine immunity to better understand disease resistance of food-producing dairy species. Diseases of livestock are a major problem for modern agriculture affecting animal and human health. The immune system is composed of genetically regulated cells and molecules with specialized ability to control response to infectious disease. Understanding the biological, genetic and epigenetic relationships within the immune system can facilitate identification of individuals with superior immune response (IR) and enhanced disease resistance. To that end, we devised the first patented system identifying cattle with elevated inherent IR. With our unique ability to identify high (H), low (L) and average (A) immune responders based on Estimated Breeding Values of their antibody (AMIR) and cell-mediated immune response (CMIR) to type 1 and 2 test antigens, we have a novel tool to further examine the genes, molecules and pathways that underpin these diverse phenotypes. In fact, H responders have about half of the disease of other phenotypes requiring less use of antibiotics. Since these IR traits are heritable (h2~25%) these genes can be passed on to their offspring to improve future generations. The immune system uniquely has the ability to vary and adapt host responses to control diverse pathogens. Identifying individuals with enhanced immuno-competence, is a method to naturally improve a range of innate and adaptive defense mechanisms, as well as to improve overall animal health. However, little is known about the genes, genetic pathways, or epigenetic influences that control H, L, or A immune responses and require further investigation. Therefore the goals for this research are: 1 - To better understand how and why cattle with H, A and L-IR phenotypes differ in the nature (quality) and expression (quantity) of key IR genes and molecules. Improved understanding of these differences will lead to better comprehension of disease resistance in important food-producing species, as well as development of new tools to improve animal health. 2- To improve knowledge of gene expression associated with these IR phenotypes and learn about the epigenetic marks on the DNA that regulate their expression. Our recent data show epigenetic regulation of key bovine cytokines and we hypothesize this will extend to other genes and account for some of the variation between these IR phenotypes. This combined genetic and biological research, utilizing individuals with known IR phenotypes based on their breeding values, provides a unique opportunity to study bovine immunity. This approach allows knowledge expansion regarding the various factors which dictate variation in immune responsiveness helping to ensure animal health and well-being in an important milk and meat producing species. These results are expected to also relate to other biological systems.