ANIHWA call2: Understanding mucosal immunology and co-infections in the chicken to drive vaccine strategies

尽管疫苗在家禽中的使用量比在任何其他养殖物种中都要大，但疫苗产生保护的机制，特别是在粘膜表面的机制，人们还知之甚少。许多制约禽类生产力和福利的疾病会影响呼吸道，而且是多因素的。需要更好地了解呼吸道对细菌和病毒感染、混合感染和疫苗的反应，以控制地方性生产疾病。在全球需求不断增加的时候，禽致病性大肠杆菌(APEC)会引起严重的呼吸道和系统性疾病，威胁粮食安全和禽类福利。感染通常涉及败血症、内脏发炎和鸡蛋产量/质量下降，并因早期死亡、生产力下降和产品报废而损失。自由放养生产系统的扩大将使禽类更多地暴露在与形成社会等级相关的环境病原体、压力和伤害中，从而增加大肠杆菌病的发病率。重要的是，亚太经合组织感染往往与呼吸道病毒感染有关。APEC(联合)感染过程中宿主-病原体相互作用的性质和后果还知之甚少。APEC的毒力因子、联合感染的拮抗或协同作用以及免疫和耐药的基础都是模糊的。欧共体范围内对预防性使用抗生素和可传播耐药性的禁令使家禽容易受到APEC感染。现有疫苗提供的保护有限。该项目将促进对禽类呼吸道粘膜免疫反应的了解。它将提供对呼吸道免疫系统的全面描述，导致研究免疫反应的新工具，并改善对肺部抗原提呈的机制和位置的理解。因此，我们将确定APEC感染的耐药性和易感性的相关性，以及病毒感染对APEC感染结局的影响。通过使用转基因鸡，我们将进一步描述抗原提呈细胞和体液免疫在APEC感染和疫苗接种中的作用，例如通过我们独特的MacRed鸡(在这些鸡中，所有单核吞噬细胞系的细胞(巨噬细胞、单核细胞和树突状细胞)都表达由鸡CSF-1受体驱动的荧光蛋白)和免疫球蛋白敲除鸡(缺乏B细胞受体，从而缺乏抗体)。

Despite the fact that vaccine use in poultry is greater than in any other farmed species, the mechanisms by which they induce protection, particularly at mucosal surfaces, are poorly understood. Many diseases constraining avian productivity and welfare affect the respiratory tract and are multi-factorial. A better understanding of responses in the respiratory tract to bacterial and viral infections, co-infections and vaccines is needed to control endemic production diseases.Avian pathogenic Escherichia coli (APEC) cause severe respiratory and systemic disease, threatening food security and avian welfare at a time of increasing global demand. Infections frequently involve sepsis, inflammation of internal organs and reduced egg yield/quality, with losses through early mortality, reduced productivity and product condemnation. The expansion of free-range production systems will increase the incidence of colibacillosis through greater exposure of birds to environmental pathogens, stress and injury associated with forming a social hierarchy. Importantly, APEC infections are frequently associated with respiratory viral infections. The nature and consequences of host-pathogen interactions during APEC (co-)infections are poorly understood. Virulence factors of APEC, antagonistic or synergistic effects of co-infection and the basis of immunity and resistance are ill-defined. The EC-wide ban on prophylactic antibiotic use and transmissible resistance render poultry susceptible to APEC infection. Existing vaccines confer limited protection. This project will advance understanding of mucosal immune responses in the avian respiratory tract. It will provide a comprehensive description of the respiratory tract immune system, leading to new tools to study immune responses and improved understanding of the mechanism and site of antigen presentation in the lung. We will thereby identify correlates of resistance and susceptibility to, and the impact of viral infections on the outcome of, APEC infection. Using transgenic chickens we will further characterise the role of antigen-presenting cells and humoral immunity during APEC infection and vaccination, for example by using our unique MacRed chickens (in which all cells of the mononuclear phagocyte lineage (macrophages, monocytes and dendritic cells) express a fluorescent protein driven by the chicken CSF-1 receptor), and immunoglobulin knock-out chickens (which lack the B cell receptor and thus antibody).