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

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This researchaddresses genetic and epigenetic mechanisms that control bovine immunity tobetter understand disease resistance of food-producing dairy species.Diseases of livestock are a major problem for modern agriculture affectinganimal and human health. The immune system is composed of geneticallyregulated cells and molecules with specialized ability to control response toinfectious disease. Understanding the biological, genetic and epigeneticrelationships within the immune system can facilitate identification ofindividuals with superior immune response (IR) and enhanced disease resistance.To that end, we devised the first patented system identifying cattle withelevated inherent IR. With our unique ability to identify high (H), low (L) andaverage (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 thatunderpin 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 thisresearch are: 1 - To better understand how and why cattle with H, A and L-IR phenotypes differ in thenature (quality) and expression (quantity) of key IRgenes and molecules. Improved understanding of these differences will lead tobetter comprehension of disease resistance in important food-producing species, as wellas 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 wehypothesize this will extend to other genes and account for some of thevariation between these IR phenotypes.This combined genetic and biological research, utilizing individuals with knownIR phenotypes based on their breeding values, provides a uniqueopportunity to study bovine immunity. This approach allows knowledge expansionregarding the various factors which dictate variation in immune responsivenesshelping to ensure animal health and well-being in an important milk and meat producingspecies. These results are expected to also relate to other biological systems.