Implications and future work

The research undertaken in this thesis has implications for the prevention and treatment of infectious and metabolic disease during the transition period. Our improved understanding of the temporal ‘dampening’ of innate immune responses around calving creates an opportunity to improve innate immune function during the transition period. Treatment methods that could ‘boost’ innate immune function (e.g., G-CSF) during the time when cows are at greatest risk of infectious disease might be beneficial in a grazing system. Furthermore, the research presented in Chapter 4 reiterates that the current BCS targets and nutritional guidelines for managing transition cows in a grazing system (Roche et al., 2013a; b) are optimal for innate immune health. The differences in exosomal cargo in animals divergent in their metabolic health phenotype support the possibility of identifying specific circulating markers of metabolic disease. Metabolic stress negatively influences tissue function (e.g., ovarian, uterine, brain, leukocytes, etc.) due to oxidative damage (Sordillo and Aitken, 2009). If exosomes regulate this metabolic stress-related damage, a cure may lie in exosomes. Future implications include the use of exosomes to treat metabolic and/or

infectious disease by alleviating metabolic stress through immunomodulatory mechanisms. A subsequent investigation may include the co-culture of exosomes from metabolically- divergent cows with white blood cells or whole blood and compare responses to an immunogenic challenge. This would help elucidate the extent of the immunomodulatory capacity of exosomes in dairy cows for the development of potential treatments. Further directions also include the use of immunomodulatory agents (e.g., granulocyte colony stimulating factor), which would improve neutrophil number and function to alieviate immunological stress over the calving period and improve cow health and well-being. Further research could investigate these immunomodulatory mechanisms combined with optimised feeding and management strategies, which would result in improved health during the period of greatest risk of disease.

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