Understanding resistance and differential vaccine responses to Eimeria in the chicken - novel biomarkers and genetic control.

了解鸡对艾美耳球虫的耐药性和差异疫苗反应 - 新型生物标志物和遗传控制。

• 批准号: BB/L004003/1
• 负责人: David Hume
• 金额: $ 49.55万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FL004003%2F1
• 关键词: Understanding; resistance; differential; vaccine; responses

One of the main underpinning factors for a profitable large-scale poultry industry is the fact that the disease coccidiosis, caused by species of the protozoan parasite Eimeria, is controlled primarily through the use of drugs, or coccidiostats. Vaccines do exist, but these are currently primarily produced by passage of Eimeria through birds and therefore not a cheap nor practical solution to replace coccidostats. Reliance on a single main control measure is not ideal, particularly with political pressure in some parts of the world to ban the use of coccidiostats.Resistance to Eimeria infection has long been known in inbred lines of chickens, but attempts to map this have been largely unsuccessful. Chromosomes associated with resistance have been identified, but we have yet to identify causative genes, or better still causative mutations. Differential responses to vaccines have also been described, presumably due to similar mechanisms, although this has yet to be formally proven. Resistance has always been described as oocyst output - the fewer oocysts excreted, the more resistant the bird. However, resistance is associated with a stronger innate and adaptive immune response in these birds, and it is unclear, particularly in broilers, if this stronger immune response compromises other parameters, such as feed conversion efficiency (FCE). In other words, do birds that produce fewer oocysts, due to a stronger gut immune response, perform better than birds that produce more oocysts, or is the obverse the case?We plan to revisit mapping disease resistance, and differential responses to vaccines, using modern techniques, in particular the newly available 600K SNP chip. Similarly to funded work on Campylobacter resistance, we will use both inbred birds in a backcross design, and commercial birds in a genome-wide association study, or GWAS, experiment. We will then assess FCE in resistant versus susceptible birds.The adaptive immune response is that which clears the pathogen causing the infection, and delivers immunological memory against reinfection. For many years, the adaptive immune response has been split into two arms, each involving a different subset of CD4+ Thelper cells. Th1 responses control infection with intracellular pathogens, such as viruses. Th2 responses control infections with extracellular pathogens such as worms. Adaptive responses are now known to be more complicated, with more subsets of CD4+ T cells involved.It is well established that infection with Eimeria, an obligate intracellular pathogen, requires a strong inflammatory, Th1 response to control it. However, little has been done recently to investigate the role, if any, of other T cell subsets which have only recently become known in mammals and for which reagents have only recently become available in the chicken - i.e. Th17, Th9 and Treg. We will investigate these arms of the adaptive immune response in both the response to primary infection and to vaccination, with the expectation that this will lead to novel tools to defining disease biomarkers and phenotypes.

一个有利可图的大规模家禽业的主要基础因素之一是，由原生动物寄生虫艾美耳球虫属物种引起的球虫病主要通过使用药物或抗球虫药来控制。疫苗确实存在，但这些疫苗目前主要是通过艾美耳球虫通过鸟类产生的，因此不是替代球虫的廉价且实用的解决方案。依靠单一的主要控制措施是不理想的，特别是在世界某些地区存在禁止使用抗球虫药的政治压力的情况下。与耐药性相关的染色体已经被确定，但我们还没有确定致病基因，或者更好的是致病突变。对疫苗的不同反应也有描述，可能是由于类似的机制，尽管这尚未得到正式证实。抵抗力一直被描述为卵囊输出-排泄的卵囊越少，鸟的抵抗力越强。然而，抗性与这些鸟类中更强的先天性和适应性免疫应答相关，并且尚不清楚，特别是在肉鸡中，这种更强的免疫应答是否会损害其他参数，例如饲料转化效率（FCE）。换句话说，由于肠道免疫反应更强，产生更少卵囊的鸟类比产生更多卵囊的鸟类表现更好，还是相反？我们计划利用现代技术，特别是新推出的600 K SNP芯片，重新绘制疾病抗性和对疫苗的不同反应。与弯曲杆菌抗性的资助工作类似，我们将在回交设计中使用近交系鸟类，并在全基因组关联研究（GWAS）实验中使用商业鸟类。然后我们将评估FCE在抗性和易感鸟类中的作用。适应性免疫反应是清除引起感染的病原体，并提供免疫记忆以防止再次感染。多年来，适应性免疫应答被分为两个分支，每个分支涉及不同的CD 4+辅助细胞亚群。Th 1应答控制细胞内病原体如病毒的感染。Th 2应答控制细胞外病原体如蠕虫的感染。适应性反应现在已知是更复杂的，涉及更多的CD 4 + T细胞亚群。它是公认的艾美耳球虫，一种专性细胞内病原体感染，需要一个强烈的炎症，Th 1反应来控制它。然而，最近很少有人做调查的作用，如果有的话，最近才在哺乳动物中发现的其他T细胞亚群，以及最近才在鸡中获得的试剂-即Th 17，Th 9和Treg。我们将研究这些适应性免疫反应的手臂在对原发性感染和疫苗接种的反应中，期望这将导致定义疾病生物标志物和表型的新工具。

项目成果

Quantitative real-time PCR (qPCR) for Eimeria tenella replication--Implications for experimental refinement and animal welfare.

• DOI: 10.1016/j.parint.2015.06.010
• 发表时间: 2015-10
• 期刊: Parasitology international
• 影响因子: 1.9
• 作者: Nolan MJ;Tomley FM;Kaiser P;Blake DP
• 通讯作者: Blake DP

Effects of Eimeria tenella infection on chicken caecal microbiome diversity, exploring variation associated with severity of pathology.

• DOI: 10.1371/journal.pone.0184890
• 发表时间: 2017
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Macdonald SE;Nolan MJ;Harman K;Boulton K;Hume DA;Tomley FM;Stabler RA;Blake DP
• 通讯作者: Blake DP

Analysis of the function of IL-10 in chickens using specific neutralising antibodies and a sensitive capture ELISA.

• DOI: 10.1016/j.dci.2016.04.016
• 发表时间: 2016-10
• 期刊: Developmental and comparative immunology
• 影响因子: 2.9
• 作者: Wu Z;Hu T;Rothwell L;Vervelde L;Kaiser P;Boulton K;Nolan MJ;Tomley FM;Blake DP;Hume DA
• 通讯作者: Hume DA