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Infection and immunity in the bovine genital tract

牛生殖道的感染和免疫

基本信息

批准号：
BB/F005121/1
负责人：
Iain Sheldon
金额：
$ 22.12万
依托单位：
Royal Veterinary College
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2007
资助国家：
英国
起止时间：
2007 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FF005121%2F1
关键词：
Infection immunity bovine genital tract

项目摘要

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.

产后子宫感染是奶牛最常见的地方病之一，可导致不孕不育、扑杀增多、痛苦不堪。奶牛在哺乳动物中是值得注意的，因为产犊后子宫细菌污染无处不在，高达40%的动物会患上子宫疾病。子宫疾病的诊断很简单，但疾病的发病率正在增加。在过去的30年里，治疗方法几乎没有改变，即使在临床症状消失后，动物仍然不能生育。然而，虽然一些动物患有严重的疾病，但另一些动物在产后有效地将细菌从子宫中清除，不会发展成疾病，并且具有很高的繁殖力。悬而未决的问题是：细菌是如何被子宫内的免疫系统检测到的，为什么一些牛如此容易患病；细菌是如何导致不孕的；以及如何减少子宫病的影响？该项目的目的是确定奶牛子宫感染相关不孕症的分子和细胞机制。目的是：1.在子宫疾病结局不同的动物中，建立子宫感染和免疫相关基因的差异调控。2.检测生殖组织对两种关键细菌(大肠杆菌、化脓性隐秘杆菌)及其病原体相关分子的免疫应答及对子宫、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农民的疾病成本，提高了奶牛业的可持续性。3.通过减少疾病和对生产供人食用的牛奶的动物进行治疗来减少对食物链的影响。4.通过减少多产奶牛产奶来提高环境的可持续性，从而减少温室气体排放，包括每年减少113吨二氧化碳排放。为了推动该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健康公司建立了合作伙伴关系，并利用与来自英国、美国和意大利的国际专家的合作。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Lipopolysaccharide initiates inflammation in bovine granulosa cells via the TLR4 pathway and perturbs oocyte meiotic progression in vitro.

DOI：
10.1210/en.2011-1124
发表时间：
2011-12
期刊：
Endocrinology
影响因子：
4.8
作者：
Bromfield JJ;Sheldon IM
通讯作者：
Sheldon IM

Signal transducer and activator of transcription-3 licenses Toll-like receptor 4-dependent interleukin (IL)-6 and IL-8 production via IL-6 receptor-positive feedback in endometrial cells.

DOI：
10.1038/mi.2015.131
发表时间：
2016-09
期刊：
Mucosal immunology
影响因子：
8
作者：
Cronin JG;Kanamarlapudi V;Thornton CA;Sheldon IM
通讯作者：
Sheldon IM

Expression of genes associated with immunity in the endometrium of cattle with disparate postpartum uterine disease and fertility.

DOI：
10.1186/1477-7827-7-55
发表时间：
2009-05-29
期刊：
Reproductive biology and endocrinology : RB&E
影响因子：
0
作者：
Herath S;Lilly ST;Santos NR;Gilbert RO;Goetze L;Bryant CE;White JO;Cronin J;Sheldon IM
通讯作者：
Sheldon IM

Defining postpartum uterine disease and the mechanisms of infection and immunity in the female reproductive tract in cattle.