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.

大规模家禽养殖业盈利的主要基础因素之一是，由原生动物寄生虫艾美耳球虫引起的球虫病主要通过使用药物或抗球虫药物来控制。疫苗确实存在，但目前主要是通过艾美耳球虫通过禽类来生产的，因此不是取代球虫药物的廉价和实用的解决方案。依赖单一的主要控制措施是不理想的，特别是在世界一些地区禁止使用球虫抑制剂的政治压力下。对艾美耳球虫感染的抵抗力在近交系鸡中早已为人所知，但绘制这一图的尝试基本上没有成功。与抗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，或者更好地说，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，尽管这一点尚未得到正式证实。抵抗力一直被描述为卵囊输出--排泄的卵囊越少，鸟类的抵抗力就越强。然而，在这些禽类中，抵抗力与更强的先天和获得性免疫反应有关，目前还不清楚，特别是在肉鸡中，这种更强的免疫反应是否会损害其他参数，如饲料转化效率(FCE)。换句话说，由于肠道免疫反应较强，产生卵囊较少的禽类表现是否优于产生卵囊较多的禽类，抑或情况正好相反？我们计划利用现代技术，特别是最新推出的600K SNP芯片，重新探讨绘制抗病能力和对疫苗的差异反应图。类似于资助的弯曲杆菌抗性研究工作，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中使用商业鸟类。然后我们将评估抵抗和敏感鸟类的FCE。适应性免疫反应是清除导致感染的病原体，并提供针对再次感染的免疫记忆。多年来，获得性免疫反应被分成两只手臂，每只手臂都涉及不同的CD4+辅助性细胞亚群。Th1反应控制细胞内病原体的感染，如病毒。Th2反应控制着对蠕虫等细胞外病原体的感染。现在已知适应性反应更复杂，涉及更多的CD4+T细胞亚群。众所周知，感染艾美耳球虫需要强烈的炎症反应，Th1反应来控制它。然而，最近很少有人研究其他T细胞亚群的作用，如果有的话，这些T细胞亚群最近才在哺乳动物中为人所知，其试剂最近才在鸡中获得--即Th17、Th9和Treg。我们将研究适应性免疫反应在对初次感染和疫苗接种的反应中的这些手臂，期望这将导致定义疾病生物标记物和表型的新工具。

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