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比在任何其他养殖物种中都要多，但它们诱导保护的机制，特别是在粘膜表面，却知之甚少。许多限制禽类生产和福利的疾病影响呼吸道，并且是多因素的。为了控制地方性生产疾病，需要更好地了解呼吸道对细菌和病毒感染、合并感染和疫苗的反应。禽致病性大肠杆菌（APEC）引起严重的呼吸道和全身疾病，在全球需求不断增加的情况下威胁着粮食安全和禽类福利。感染通常包括败血症、内脏炎症和鸡蛋产量/质量下降，损失包括早期死亡、生产力下降和产品谴责。自由放养生产系统的扩大将增加大肠杆菌病的发病率，因为鸟类更多地暴露于环境病原体、压力和与形成社会等级有关的伤害。重要的是，APEC感染经常与呼吸道病毒感染有关。在APEC（共）感染期间，宿主-病原体相互作用的性质和后果尚不清楚。APEC的毒力因子、共感染的拮抗或协同效应以及免疫和耐药的基础尚不明确。欧盟范围内禁止预防性抗生素使用和传染性耐药性使家禽易受亚太经合组织感染。现有疫苗的保护作用有限。本项目将促进对禽呼吸道粘膜免疫反应的认识。它将提供呼吸道免疫系统的全面描述，为研究免疫反应提供新的工具，并提高对肺中抗原呈递机制和部位的理解。因此，我们将确定耐药性和易感性的相关性，以及病毒感染对APEC感染结果的影响。使用转基因鸡，我们将进一步表征抗原呈递细胞和体液免疫在APEC感染和疫苗接种中的作用，例如使用我们独特的MacRed鸡（其中所有单核吞噬细胞谱系的细胞（巨噬细胞，单核细胞和树突状细胞）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细胞受体和抗体）。

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).