Mechanisms that regulate bovine adaptive immune responses and impact disease outcome

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Livestock diseases are a concern for modern agriculture, affecting both animal and human health. This research seeks to evaluate mechanisms that regulate bovine immunity with a goal to improve dairy health. The immune system is composed of cells and molecules that help control infectious disease. A better understanding of the mechanisms that regulate the immune system is expected to facilitate identification of individuals with superior immunity, and help in the discovery of novel therapeutics for animal health. Peripartum cows are under physical and metabolic pressure due to the stressful transition through late pregnancy into high volume milk production. Disease occurence peaks at this time, affecting milk quantity, quality and safety. Previously, we and others have shown that peripartum immune responses (IR) are suboptimal and this contributes, at least in part, to increased disease. However, little is known about the factors that regulate peripartum immunity, and only a handful of groups having expertise in both bovine immunology and genetics are investigating ways to improve immunity to important cattle diseases. Recent studies of mouse and man show that T-cell responses are under both genetic and epigenetic influences, including T-cell differentiation into T-helper 1 and T-helper 2 cells that dominate in type 1 and 2 IR, respectively. Type 1 responses are predominately cell-mediated, important to control intracellular pathogens, whereas type 2 responses are mainly antibody-mediated dominating in control of extracellular pathogens. The ability to adequately produce both responses is critical, but often individuals will have a bias in one direction or another, and these biases are known to shift during pregnancy. Relatively little is known about the control of type 1 and type 2 IR, particularly changes during the bovine peripartum period. Therefore this proposal is designed to investigate changes in bovine type 1 and 2 immune responses before, during and after parturition using genetic and epigenetics tools to better understand immune regulation. The core hypothesis being that alterations in bovine peripartum immunity are due to shifts in type 1 and type 2 IR that are influenced by both genetic and epigenetic factors.