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

这项研究解决了控制牛免疫的遗传和表观遗传机制，以更好地了解生产食物的奶牛物种的抗病能力。牲畜疾病是影响动物和人类健康的现代农业的一个主要问题。免疫系统由基因调控的细胞和分子组成，具有控制对传染病反应的特殊能力。了解免疫系统内的生物、遗传和表观遗传关系，有助于识别具有优越免疫反应（IR）和增强抗病能力的个体。为此，我们设计了第一个专利系统，用于识别具有较高固有IR的牛。凭借我们独特的能力，根据抗体（AMIR）的估计育种值和细胞介导的免疫反应（CMIR）对1型和2型测试抗原识别高(H)，低(L)和*平均(A)免疫应答者，我们有一个新的工具来进一步检查支撑这些不同表型的基因，分子和途径。事实上，H应答者有大约一半的其他表型的疾病需要较少使用抗生素。由于这些IR特征是可遗传的（h2~25%），这些基因可以传递给他们的后代，以改善后代。******免疫系统具有独特的能力来改变和适应宿主的反应来控制不同的病原体。识别具有增强免疫能力的个体，是一种自然地改善一系列先天和适应性防御机制以及改善整体动物健康的方法。然而，关于控制H、L或A免疫反应的基因、遗传途径或表观遗传影响知之甚少，需要进一步研究。******因此，本研究的目标是：******1 -更好地了解H， A和L-IR表型的牛在关键IR基因和分子的性质（质量）和表达（数量）上的差异。加深对这些差异的了解，将有助于更好地了解重要粮食生产物种的抗病能力，以及开发改善动物健康的新工具。******2-提高与这些IR表型相关的基因表达的知识，并了解DNA上调节其表达的表观遗传标记。我们最近的数据显示了关键的牛细胞因子的表观遗传调控，我们假设这将扩展到其他基因，并解释这些IR表型之间的一些差异。******这种结合遗传和生物学的研究，利用基于其育种价值的已知IR表型的个体，为研究牛免疫提供了独特的机会。这种方法可以扩展有关决定免疫反应变化的各种因素的知识，有助于确保重要的牛奶和肉类生产物种的动物健康和福祉。预计这些结果也适用于其他生物系统。****** ****

This research*addresses genetic and epigenetic mechanisms that control bovine immunity to*better understand disease resistance of food-producing dairy species.*Diseases of livestock are a major problem for modern agriculture affecting*animal and human health. 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 devised the first patented system identifying cattle with*elevated inherent IR. With our unique ability to identify high (H), low (L) and*average (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 that*underpin 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 this*research are: ******1 - To better understand how and why cattle with H, A and L-IR phenotypes differ in the*nature (quality) and expression (quantity) of key IR*genes and molecules. Improved understanding of these differences will lead to*better comprehension of disease resistance in important food-producing species, as well*as 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 we*hypothesize this will extend to other genes and account for some of the*variation between these IR phenotypes.******This combined genetic and biological research, utilizing individuals with known*IR phenotypes based on their breeding values, provides a unique*opportunity to study bovine immunity. This approach allows knowledge expansion*regarding the various factors which dictate variation in immune responsiveness*helping to ensure animal health and well-being in an important milk and meat producing*species. These results are expected to also relate to other biological systems.****** ****