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.

有利可图的大规模家禽行业的主要基础因素之一是，由原生动物寄生虫嗜酸酯物种引起的疾病coccidiosis主要是通过使用药物或coccidiostats来控制的。确实存在疫苗，但是目前这些疫苗主要是由伊滨通过鸟类通过鸟类而产生的，因此不是替代球骨的廉价或实际解决方案。依赖单一主要控制措施并不理想，尤其是在世界某些地区禁止使用coccidiostat的政治压力的情况下。对埃米丽感染的抵抗力在鸡的近交系列中一直是众所周知的，但是试图映射这一数字的试图在很大程度上取得了很大的成功。已经鉴定出与抗性相关的染色体，但是我们尚未鉴定出致病基因，或者更好的仍然是病因突变。还描述了对疫苗的差异反应，大概是由于类似的机制，尽管尚未正式证明这一点。电阻一直被描述为卵囊输出 - 卵囊排出越少，鸟类越耐药。然而，抗性与这些鸟类的先天和适应性免疫反应相关，目前尚不清楚，尤其是在肉鸡中，如果这种更强的免疫反应会损害其他参数，例如饲料转化效率（FCE）。换句话说，由于肠道免疫反应较强，产生卵囊的鸟类是否比产生更多卵囊的鸟类表现更好，还是正面的情况？我们计划重新审视抗疾病的耐药性和对疫苗的差异反应，并使用现代技术，特别是新近可用的600K SNP SNP芯片。与弯曲杆菌抵抗性的资助工作类似，我们将在反杂交设计中使用近交鸟，而在全基因组协会研究中或GWAS进行实验中使用商业鸟类。然后，我们将评估耐药性与易感鸟类的FCE。适应性免疫反应是清除导致感染的病原体，并提供免疫记忆，以防止再感染。多年来，自适应免疫反应已被分为两个臂，每个臂都涉及不同的CD4+细胞子集。 Th1反应控制着细胞内病原体（例如病毒）感染。 TH2反应控制着细胞外病原体（例如蠕虫）的感染。现在已知自适应反应更为复杂，涉及更多的CD4+ T细胞子集。它已经很好地确定，具有强大的细胞内病原体Eimeria的感染需要强烈的炎症性TH1反应才能控制它。但是，最近几乎没有做过其他T细胞子集（如果有的话），这些T细胞子集直到最近才在哺乳动物中闻名，并且试剂直到最近才在鸡肉中使用-Th17，Th9和Treg。我们将在对原发性感染和疫苗接种的反应中调查自适应免疫反应的这些臂，并期望这将为定义疾病生物标志物和表型的新工具提供新的工具。

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

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

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