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

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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