Host Resistance to Avian Pathogenic E. coli

禽大肠杆菌病是一种严重的传染性疾病，在世界范围内严重影响家禽的健康、福利和生产力。它是影响火鸡、蛋鸡和肉鸡的最常见传染病。感染通常由吸入含有禽致病性大肠杆菌（APEC）的粪便粉尘引起，通常继发于呼吸道病毒或支原体感染。新生儿免疫系统的不成熟以及性成熟开始时或压力下免疫功能的抑制也是关键的风险因素，尽管这些因素如何作用于呼吸道粘膜尚不清楚。呼吸窘迫是常见的以下APEC感染和细菌经常易位到血液和内脏器官，造成各种问题，包括败血症，肝炎和蜂窝织炎。损失是通过增加死亡率、降低生产率、屠宰时废弃尸体以及降低蛋鸡产蛋量和蛋质量而引起的。问题的规模是巨大的。在英国，最近对4个肉鸡群进行了为期4周的每周抽样调查，发现39%的死禽有大肠杆菌病的证据。对肉鸡放置后2-3天的死亡原因进行的单独分析发现，70%的死禽有大肠杆菌病的证据。虽然该病的发病率因地理位置、物种和生产系统而异，但一个共同的特点是与病禽细菌分离物相关的APEC的高度多样性。E.本研究的目的是明确禽类对呼吸道大肠杆菌感染的抗性的遗传学和免疫学基础，为疫苗的设计和基因组选择策略提供依据。在我们的综合和协同项目中，我们将利用这两个国家独特的近交系鸡株，它们对APEC的抗性不同，分析转基因鸡，其中所有髓系细胞都表达荧光蛋白，以帮助对APEC感染的细胞进行分选和表型分析，使用最先进的方法来定义感染细胞的转录组，并将抗性与鸟类基因型相关联，并验证选定的研究成果，以便将其转化为工业应用。迫切需要改善对这种关键的地方性禽类疾病的控制，但对禽呼吸道对APEC的反应和遗传宿主抗性的基础的研究非常缺乏。我们对鸡和APEC之间宿主-病原体相互作用的基因组、分子和细胞表征将确定可用于通过兽医和育种策略增强对APEC抗性的关键控制点。我们的长期目标是通过制定基于对宿主对E.大肠杆菌感染。

Avian colibacillosis is a severe and recalcitrant disease that constrains the health, welfare and productivity of poultry worldwide. It is the most common infectious disease affecting turkeys, layers, and broilers. Infections are frequently initiated by inhalation of faecal dust containing avian pathogenic Escherichia coli (APEC) and are often secondary to respiratory viral or Mycoplasma infections. Immaturity of the immune system in neonates and suppression of immune function at the onset of sexual maturity or under stress are also key risk factors, though how such factors act at the respiratory mucosa is ill-defined. Respiratory distress is common following APEC infection and the bacteria often translocate to the blood and internal organs, causing a variety of problems, including sepsis, hepatitis, and cellulitis. Losses are incurred via increased mortality, reduced productivity, condemnation of carcasses at slaughter, and decreased egg yield and egg quality in layers. The scale of the problem is vast. In the United Kingdom, a recent survey of 4 broiler flocks sampled weekly for 4 weeks found evidence of colibacillosis in 39% of dead birds. A separate analysis of causes of death 2-3 days after placement of broiler chicks found evidence of colibacillosis in 70% of dead birds. Although the incidence of the disease varies with geographical location, species and production system, a common feature is the high diversity of APEC associated with the bacterial isolates from diseased birds. E. coli diseases result in annual multimillion pound losses by the worldwide poultry industry.Our goal in this project is to define the genetic and immunological basis of avian resistance to respiratory Escherichia coli infection so as to inform the design of vaccines and genomic selection strategies. In our integrated and synergistic project, we will exploit unique inbred chicken lines in both countries that differ in resistance to APEC, analyze transgenic chickens in which all cells of the myeloid lineage express a fluorescent protein to aid sorting and phenotyping of APEC-infected cells, use state-of-the-art methods to define the transcriptome of infected cells and associate resistance with bird genotype, and validate selected research findings for translation into industry application. An urgent need exists to improve control of this key endemic avian disease, yet there is a striking paucity of research on avian airway responses to APEC and the basis of heritable host resistance. Our genomic, molecular and cellular characterization of the host-pathogen interactions between chickens and APEC will identify critical control points that can be used to enhance resistance to APEC through veterinary and breeding strategies. Our long-term goal is to reduce the occurrence and negative impact of this disease on the poultry industry through development of control strategies that are based on a thorough understanding of the host's functional responses to E. coli infection.