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Host factors in determining resistance to cryptosporidiosis in cattle

决定牛隐孢子虫病抗性的宿主因素

基本信息

批准号：
BB/M012751/1
负责人：
Elisabeth Innes
金额：
$ 58.77万
依托单位：
Moredun Research Institute
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2015
资助国家：
英国
起止时间：
2015 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FM012751%2F1
关键词：
Host factors determining resistance cryptosporidiosis

项目摘要

Cryptosporidium parasites are the most important cause of enteric disease in young cattle in UK and worldwide and are also one of the leading causes of infant diarrhoea in humans [1]. Neonatal calves are very vulnerable to cryptosporidiosis resulting in significant morbidity due to severe diarrhoea and dehydration and there are increasing reports of mortality. Cryptosporidiosis is a challenge to control as infected animals shed billions of infective, long lived oocysts into the environment and these are a source of infection for other animals as well as people. The disease has emerged as an increasing problem in beef suckler units, and livestock industry leaders are very concerned about the lack of safe and effective treatments or vaccines available to help prevent and control cryptosporidiosis and have given their strong support for this proposal. Our understanding of the host-pathogen interactions that determine disease outcome is limited. Neonatal calves are very vulnerable to infection and often exhibit clinical disease, whereas older calves are more resistant. The factors involved in determining this age-related susceptibility are unclear and this project aims to address the host factors involved in resistance to cryptosporidiosis by applying novel and innovative in vivo, ex vivo and in vitro technologies to examine in detail the host parasite interaction during acute infection and recovery in calves.One of the constraints for improving our understanding of the factors that determine disease resistance has been the lack of simple research systems that permit the detailed analysis of host parasite interactions. The rodent model is an acknowledged poor comparator for clinical disease in cryptosporidiosis in particular, and the capability for culturing Cryptosporidium parasites in vitro is very limited. This project aims to tackle these gaps in capability by utilising a combination of in vivo and in vitro bovine systems to assess innate and adaptive cellular immune responses and examine the interaction of Cryptosporidium with gut epithelial cells. In addition, innovative 3D bovine gut organoid in vitro culture systems will be applied to enable a detailed analysis of host parasite interactions in the bovine gut epithelium. Data derived from the experimental studies will be validated by comparison to similar data obtained from naturally infected calves on a study farm.This project will provide the fullest exploration yet of how cattle resist infection with Cryptosporidium parasites. A detailed account of the host responses involved will provide an important knowledge platform that will enable the development of vaccines to aid disease prevention and the identification of relevant biomarkers that will enable selective breeding programmes to improve resilience. In addition, the development of novel in vitro bovine systems would revolutionise our capability to study host-pathogen interactions with Cryptosporidium minimising the need for use of animal models.Outputs from the project will be of interest to the animal health industry, livestock producers, environmental and public health workers and to academic researchers. The development of effective control strategies will have a significant impact on the sustainable efficiency of animal production, safeguard food security, improve animal health and welfare, reduce waste and environmental contamination and improve public and environmental health. [1] Streipen B (2013) Nature 503:189

隐孢子虫寄生虫是英国和全世界幼牛肠道疾病的最重要原因，也是人类婴儿腹泻的主要原因之一[1]。新生犊牛非常容易感染隐孢子虫病，导致严重腹泻和脱水导致严重发病，并且死亡率的报告不断增加。隐孢子虫病的控制是一项挑战，因为受感染的动物会向环境中排放数十亿个具有感染性的、寿命较长的卵囊，而这些卵囊是其他动物和人类的感染源。这种疾病已成为肉牛饲养场中日益严重的问题，畜牧业领导者非常关注缺乏安全有效的治疗方法或疫苗来帮助预防和控制隐孢子虫病，并对该提案给予了大力支持。我们对决定疾病结果的宿主-病原体相互作用的理解是有限的。新生犊牛非常容易受到感染，并且经常表现出临床疾病，而老年犊牛的抵抗力更强。决定这种与年龄相关的易感性的因素尚不清楚，该项目旨在通过应用新颖和创新的体内、离体和体外技术，详细检查小牛急性感染和恢复期间宿主寄生虫的相互作用，来解决参与隐孢子虫病抗性的宿主因素。提高我们对决定抗病性的因素的理解的限制之一是缺乏允许进行详细分析的简单研究系统宿主寄生虫相互作用。啮齿动物模型是公认的隐孢子虫病临床疾病的较差比较器，尤其是在体外培养隐孢子虫寄生虫的能力非常有限。该项目旨在通过利用体内和体外牛系统的组合来评估先天性和适应性细胞免疫反应并检查隐孢子虫与肠上皮细胞的相互作用，从而解决这些能力差距。此外，创新的 3D 牛肠道类器官体外培养系统将用于详细分析牛肠道上皮细胞中宿主寄生虫的相互作用。来自实验研究的数据将通过与研究农场中自然感染的小牛获得的类似数据进行比较来验证。该项目将对牛如何抵抗隐孢子虫寄生虫的感染进行最全面的探索。对所涉及的宿主反应的详细描述将提供一个重要的知识平台，使疫苗的开发能够帮助疾病预防，并识别相关的生物标志物，从而使选择性育种计划能够提高抵御能力。此外，新型体外牛系统的开发将彻底改变我们研究宿主-病原体与隐孢子虫相互作用的能力，最大限度地减少对动物模型的使用。该项目的成果将引起动物保健行业、牲畜生产者、环境和公共卫生工作者以及学术研究人员的兴趣。制定有效的控制策略将对动物生产的可持续效率、保障粮食安全、改善动物健康和福利、减少废物和环境污染以及改善公众和环境健康产生重大影响。 [1] Streipen B (2013) 自然 503:189

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）

Bovine cryptosporidiosis: impact, host-parasite interaction and control strategies.

DOI：
10.1186/s13567-017-0447-0
发表时间：
2017-08-11
期刊：
Veterinary research
影响因子：
4.4
作者：
Thomson S;Hamilton CA;Hope JC;Katzer F;Mabbott NA;Morrison LJ;Innes EA
通讯作者：
Innes EA

Development of in vitro enteroids derived from bovine small intestinal crypts.

DOI：
10.1186/s13567-018-0547-5
发表时间：
2018-07-03
期刊：
Veterinary research
影响因子：
4.4
作者：
Hamilton CA;Young R;Jayaraman S;Sehgal A;Paxton E;Thomson S;Katzer F;Hope J;Innes E;Morrison LJ;Mabbott NA
通讯作者：
Mabbott NA

Development of a framework for genotyping bovine-derived Cryptosporidium parvum, using a multilocus fragment typing tool.

DOI：
10.1186/s13071-015-1107-8
发表时间：
2015-10-01
期刊：
Parasites & vectors
影响因子：
3.2
作者：
Hotchkiss EJ;Gilray JA;Brennan ML;Christley RM;Morrison LJ;Jonsson NN;Innes EA;Katzer F
通讯作者：
Katzer F

Genetic diversity and shedding profiles for Cryptosporidium parvum in adult cattle and their calves.