Investigating Mechanisms and Genes that Shape Bovine Host Defence and Impact Disease Outcome in High and Low Immune Responders Phenotypes

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Emerging and re-emerging diseases of livestock, as well as antibiotic resistance are a major problem affecting animal and human health. This research program addresses various aspects of genetic regulation of the immune system as a means to better understand disease resistance of food-producing animals. 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 have devised the first patented system to identify dairy cattle with elevated inherent IR, particularly during production when disease incidence is high and IR impaired. With our ability to identify high (H), low (L) and average (A) immune responders, it is now possible to exam in detail the genes, molecules and pathways that shape these diverse phenotypes. For example, antibody (AMIR) and cell-mediated immune response (CMIR) to type 1 and 2 test antigens indicates that dairy cattle and their offspring can be ranked based on H or L-IR and that this response is highly heritable (h2~25%). Noteworthy is that broad-based disease resistance is dependent on both AMIR and CMIR. Aspects of the innate immune system that initiate adaptive immunity also differ between individuals with these unique IR phenotypes, but need to be studied in more depth. The immune system is unique in that it has the ability to adapt host response to control a wide range of diverse pathogens. Selective breeding, simultaneously for AMIR and CMIR, based on estimated breeding values (EBVs) has been demonstrated by our group to improve a range of innate and adaptive defense mechanisms, as well as to improve overall animal health. However, we still know little about the genes, genetic pathways, or epigenetic influences that control H, L, or A immune responses. Information about the specific immunological mechanisms associated with each of these phenotypes is also scant. The core hypotheses for this research program are: 1 - Dairy cattle with H, A and L-IR phenotypes (based on EBVs) differ in the nature (eg quality) and expression (eg quantity) of key immune response genes and molecules. 2- Individuals classified as H, A or L immune responders will differ not only in their gene expression profiles but also in epigenetic marks on key immune response genes. This combined genetic and biological research program provides an original and innovative approach to study the basis of immunity in food-producing dairy cattle. The H and L-IR phenotypes are a powerful discovery method to uncover the various factors which have bovine immunity, improving animal health and food quality.