Host Resistance to Avian Pathogenic E. coli

禽大肠杆菌病是一种严重的顽固性疾病，它限制了全世界家禽的健康、福利和生产力。它是影响火鸡、蛋鸡和肉鸡的最常见的传染病。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和性成熟开始时或应激下免疫功能的抑制也是关键的危险因素，尽管这些因素如何作用于呼吸道粘膜尚不清楚。APEC感染后常见呼吸窘迫，细菌常转移到血液和内脏，引起各种问题，包括败血症、肝炎和蜂窝织炎。损失发生在死亡率增加、生产力下降、屠宰时尸体腐烂、产蛋量和蛋品质的下降等方面。这个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%的死鸟存在大肠杆菌病的证据。在放置肉鸡2-3天后对死亡原因进行的单独分析发现，有证据表明70%的死鸟存在大肠杆菌病。尽管该病的发病率因地理位置、物种和生产系统而异，但一个共同特征是与病禽分离的细菌相关的APEC高度多样性。大肠杆菌疾病导致全球家禽业每年损失数百万英镑。我们在这个项目中的目标是确定家禽对呼吸道大肠杆菌感染的抗性的遗传和免疫学基础，以便为疫苗的设计和基因组选择策略提供信息。在我们的整合和协同项目中，我们将利用两国对APEC抗性不同的独特近交系，分析转基因鸡，其中所有髓系细胞都表达荧光蛋白，以帮助APEC感染细胞的分类和表型，使用最先进的方法定义感染细胞的转录组，并将抗性与鸟类基因型联系起来，并验证选定的研究成果，以便转化为工业应用。目前迫切需要改善对这一关键地方性禽类疾病的控制，但关于禽类呼吸道对APEC的反应和宿主遗传抗性基础的研究却非常缺乏。我们对鸡与APEC之间宿主-病原体相互作用的基因组，分子和细胞特征将确定关键控制点，可以通过兽医和育种策略来增强对APEC的抗性。我们的长期目标是通过制定基于对宿主对大肠杆菌感染的功能反应的全面了解的控制策略，减少这种疾病对家禽业的发生和负面影响。

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.