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

大型家禽业盈利的主要基础因素之一是，球虫病主要是通过使用药物或抗球虫药来控制的，球虫病是由原生动物寄生虫艾美耳球虫引起的。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传播来生产的，因此不是替代灭球虫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，特别是在世界上一些地区面临禁止使用抗球虫药的政治压力的情况下。长期以来，人们已经知道自交系的鸡对艾美耳虫感染具有抵抗力，但是绘制这种抵抗力的尝试在很大程度上是不成功的。与耐药性相关的染色体已被确定，但我们尚未确定致病基因，或者更好的是致病突变。还描述了对疫苗的不同反应，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排出量——排出的卵囊越少，鸟类的抵抗力就越强。然而，在这些鸟类中，耐药性与更强的先天和适应性免疫反应有关，而且目前尚不清楚，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，如饲料转换效率（FCE）。换句话说，是否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得更好，或者情况正好相反？我们计划使用现代技术，特别是新获得的600K SNP芯片，重新绘制疾病抗性和对疫苗的差异反应。与获得资助的弯曲杆菌耐药性研究类似，我们将在回交设计中使用近亲繁殖的鸟类，并在全基因组关联研究（GWAS）实验中使用商业鸟类。然后，我们将评估耐药和易感鸟类的FCE。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，适应性免疫反应被分为两部分，每一部分涉及CD4+ Thelper细胞的不同亚群。Th1应答控制细胞内病原体（如病毒）的感染。Th2反应控制细胞外病原体（如蠕虫）的感染。目前已知适应性反应更为复杂，涉及更多CD4+ T细胞亚群。艾美耳球虫是一种专性细胞内病原体，感染艾美耳球虫需要强烈的炎性Th1反应来控制它。然而，最近很少有人研究其他的T细胞亚群的作用，如果有的话，这些细胞亚群是最近才在哺乳动物中发现的，它们的试剂也是最近才在鸡中可用的——即Th17、Th9和Treg。我们将在对原发性感染和疫苗接种的反应中研究适应性免疫反应的这些分支，期望这将导致定义疾病生物标志物和表型的新工具。

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.