Genetic and epigenetic regulation of the stress response and implications for ruminant health

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Glucocorticoids (GC) help to maintain physiological homeostasis during microbial infections, in part, by regulating the inflammatory and immune response. Circulating GC levels are tightly regulated by signals from both the immune system and hypothalamic-pituitary-adrenal (HPA) axis. It is suspected that disruption of these bi-directional communication pathways, or their dysfunction, may contribute to the pathogenesis of inflammatory diseases in livestock, and that genetics as well as maternal stress-induced epigenetic programming of the fetus influence disease susceptibility and outcome. Our group has optimized an acute bacterial endotoxin inflammatory stress (BEIS) model to study the ovine HPA response during simulated bacterial infection, and we have used this stress model to study the genetics and epigenetics of the stress response and it's relationship with the host immune response (IR) as well as behaviour. In this round of renewal, we are proposing to; 1) fine map genetic associations that were previously identified with BEIS-ranked high (HCR) and low (LCR) cortisol responding sheep in a genome-wide association study, 2) assess HCR and LCR ewe nursing behaviour and time to lamb's first feeding as indicators of lamb health potential, 3) identify associations between HPA responsiveness and mucosal immunity using various infection models, 4) identify gene pathways that are subject to BEIS programming during fetal development, and 5) assess mucosal immunity of offspring subjected to BEIS programming using various infection models. It is anticipated that the identification of genes, gene polymorphisms, and enhanced understanding of gene-by-environment interaction during fetal development will contribute to improving animal health and food quality, reducing our dependence on antibiotics in agriculture, and enhance our understanding of the pathways that regulate the neuroendocrine-immune system in mammalians.