Exploitation of new technologies to advance understanding of avian dendritic cell biology

成年生物体的血液和组织由许多细胞类型组成，包括携带氧气的红细胞和对抗疾病的免疫细胞。免疫细胞对病毒或微生物的感染作出反应，并启动细胞和分子防御机制，称为“免疫反应”。如果我们想制定疾病控制措施，如疫苗接种，了解免疫系统如何保护身体免受疾病的侵害至关重要。大多数关于免疫反应的研究都是在人类和动物模型（如小鼠）中进行的。然而，了解农场动物的免疫系统是如何工作的是非常重要的。一个关键的例子是鸡：鸡是地球上最受欢迎的食用动物，每年有超过500亿只鸡被孵化和饲养。从经济成本和动物福利的角度来看，疾病控制是鸡生产中的一个主要挑战。另一个因素是，一些禽类疾病，如禽流感，可能会感染人类，因此对人类健康构成重大挑战。从食品安全、公共卫生和消费者安全方面保护家禽业至关重要，不仅在英国，而且在全世界。增加我们对鸡的免疫系统和对疾病的免疫反应的理解的一个复杂因素是，鸟类的免疫系统与哺乳动物的免疫系统完全不同。哺乳动物的一些专门用于免疫功能的器官，如淋巴结，在鸟类中不存在，而鸟类有自己的专门免疫器官，在哺乳动物中不存在。一些免疫细胞在哺乳动物和鸟类之间是相似的，但尚不清楚这些细胞是否具有相同的功能或对产生有效的免疫反应有不同的要求。最重要的免疫细胞类型之一是单核吞噬细胞。这是一类具有许多不同功能的细胞，因此这些细胞有许多不同的子集。单核吞噬细胞的一个非常重要的功能是处理抗原物质并将其呈递给免疫系统的其他细胞，然后这些细胞可以做出适当的反应。从这个意义上说，它们将潜在病原体的性质信息传达给免疫系统的其他部分。关于什么样的细胞类型在鸟类中呈递抗原的信息很少。我们需要获得更多关于这些过程的信息，我们已经开发了一种新的工具来识别和研究这些细胞，最近发现了一种非常重要的单核吞噬细胞，称为传统或经典的树突状细胞。这是非常重要的，因为这意味着我们可以使用这些工具来充分研究这些细胞。这项研究的主要目的是（1）在不同年龄和不同组织中鉴定和功能性地鉴定鸡的常规树突状细胞（2）生产缺乏这些常规树突状细胞的基因编辑鸟类，以分离它们的特定功能（3）使用目标1中产生的基因编辑鸟类来测试它们对细菌病原体沙门氏菌的抵抗力有多重要。从长远来看，这些知识有助于我们开发更好的疫苗来预防鸡的疾病，目的是提高生产成本，生物安全和生产鸡的福利。

The blood and tissues of an adult organism consist of a number of cell types, including the red blood cells that carry oxygen and immune cells that fight disease. Immune cells respond to infection by viruses or microbes and initiate cellular and molecular defence mechanisms, known as an "immune response". An understanding of how the immune system defends the body against diseases is critically important if we want to develop disease control measures, such as vaccination. Most research on the immune response has been carried out on humans and in animal models such as mice. However, it is very important that we understand how the immune system of farm animals works. A key example of this is the chicken: the chicken is the most popular food animal on the planet, with over 50 billion being hatched and raised each year. Control of diseases is a major challenge in chicken production in terms of economic cost and animal welfare. An additional factor is that some bird diseases, such as bird flu, can potentially infect humans and are therefore a major challenge to human health. Protecting the poultry industry in terms of food security, public health and consumer safety is of paramount importance, not only in the UK, but worldwide. One complicating factor in increasing our understanding of the chicken's immune system and immune response to disease is that the bird's immune system is quite different to that of mammals. Some of the organs specialised for immune function in mammals, such as lymph nodes, are not present in birds, whereas birds have their own specialised immune organs that are not present in mammals. Some immune cells are similar between mammals and birds, but it is not known if these share the same functions or have different requirements for generation of an effective immune response. One of the most important types of immune cells are mononuclear phagocytes. These are a class of cells with many different functions and consequently there are many different subsets of these cells. One very important function of mononuclear phagocytes is to process antigen material and present it to other cells of the immune system, which can then respond appropriately. In this sense they communicate information on the nature of a potential pathogen to the rest of the immune system. There is very little information about what cell type(s) present antigen in birds. We need to gain more information on these processes and we have developed a new tools for identifying and studying these cells and have recently identified a very important type of mononuclear phagocyte which are known as conventional or classic dendritic cells. This is very important as this means that we can use these tools to fully study these cells. The main objectives of this research proposal are to (1) identify and functionally characterise chicken conventional dendritic cells in birds at different ages and in different tissues (2) produce gene edited birds that lack these conventional dendritic cells in order to isolate their specific functions (3) Use the gene edited birds generated in objective 1 to test how important they are to resistance against the bacterial pathogen Salmonella. In the longer term this knowledge help us develop better vaccines to prevent disease in chickens with the aim of improving production costs, biosecurity and welfare of production chickens