Infection and immunity in the bovine genital tract

分娩后子宫感染是奶牛最常见的地方病之一，导致不育、扑杀增加、痛苦和折磨。奶牛是哺乳动物中值得注意的，因为产犊后子宫的细菌污染无处不在，高达40%的动物会患上子宫疾病。子宫疾病的诊断是直截了当的，但发病率正在增加。在过去的30年里，治疗方法几乎没有改变，即使在临床症状消退后，动物仍然是低生育能力的。然而，虽然一些动物有严重的疾病，但其他动物在产犊后有效地消除了子宫内的细菌，不会发病，而且生育能力很强。尚未解决的问题是，子宫内的免疫系统是如何检测细菌的，以及为什么有些牛如此容易生病；细菌是如何导致不孕的；而且，怎样才能通过减少子宫疾病的影响呢？该项目的目的是确定与奶牛子宫感染相关的不孕症的分子和细胞机制。目标是：1。在不同子宫疾病结局的动物中建立与子宫感染和免疫相关基因的差异调控。2. 测量生殖组织对两种关键细菌（大肠杆菌、化脓性隐菌）及其病原体相关分子的免疫反应，以及对子宫、卵巢细胞和胚胎功能的影响。3. 确定阻断关键免疫信号通路对子宫细胞炎症反应的影响。利用所产生的关于子宫疾病的知识的预期好处是：1。通过降低子宫疾病的发病率和严重程度来改善动物福利。2. 通过减少疾病对生育力的影响和疾病对农民的成本，提高奶牛养殖的可持续性。3. 通过减少疾病和对生产供人类食用的牛奶的动物进行治疗，减少对食物链的影响。4. 通过使用更少更肥沃的奶牛生产牛奶来提高环境的可持续性，从而减少温室气体排放，包括每年节省113吨二氧化碳排放。为了推动项目知识的商业化和发展，我们与世界上最大的兽药公司辉瑞动物保健公司建立了合作伙伴关系，并与来自英国、美国和意大利的国际专家进行了合作。

Uterine infection after parturition is one of the most common endemic diseases of dairy cattle, leading to infertility, increased culling, pain and suffering. Dairy cattle are notable amongst mammals because bacterial contamination of the uterus is ubiquitous after calving and up to 40% of animals develop uterine disease. The diagnosis of uterine disease is straightforward, but the incidence of disease is increasing. The treatments have changed little over the last 30 years, and animals are still sub-fertile even after resolution of the clinical signs. However, whilst some animals have severe disease others efficiently eliminate the bacteria from the uterus after calving, don't develop disease, and are highly fertile. The unanswered questions are about how bacteria are detected by the immune system in the uterus and why some cattle are so prone to disease; how the bacteria cause infertility; and, how the impact of uterine disease can by reduced? The aim of the project is to identify the molecular and cellular mechanisms underlying the infertility associated with uterine infection in dairy cattle. The objectives are: 1. Establish the differential regulation of genes associated with uterine infection and immunity in animals with disparate uterine disease outcomes. 2. Measure the immune responses to the two key bacteria (Escherichia coli; Arcanobacterium pyogenes) and their pathogen associated molecules by reproductive tissues and the impact on the function of uterine and ovarian cells, and the embryo. 3. Determine the effect of blocking key immune signaling pathways on the uterine cell inflammatory response. The expected benefits from exploiting the knowledge generated about uterine disease are: 1. Improved animal welfare by reducing the incidence and severity of uterine disease. 2. Increased sustainability of dairy farming, by reducing the impact of disease on fertility and the cost of disease to the farmer. 3. Reducing the impact on the food chain, by reducing disease and the application of treatments in animals producing milk for human consumption. 4. Increased sustainability of the environment by producing milk from fewer more fertile cows, and thus reduce greenhouse gas emissions, including saving 113 tonnes of CO2 emissions per year. To drive commercialisation and development of the knowledge from the project we have developed a partnership with the biggest veterinary pharmaceutical company in the world, Pfizer Animal Health, as well as exploiting collaborations with international experts from the UK, USA and Italy.