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

利用新技术促进对禽树突状细胞生物学的了解

• 批准号: BB/R003653/1
• 负责人: Adam Balic
• 金额: $ 60.14万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FR003653%2F1
• 关键词: Exploitation; new; technologies; advance; understanding

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

成人有机体的血液和组织由多种细胞类型组成，包括携带氧气的红细胞和抵抗疾病的免疫细胞。免疫细胞对病毒或微生物的感染做出反应，并启动细胞和分子防御机制，称为“免疫反应”。如果我们想制定疫苗接种等疾病控制措施，那么了解免疫系统如何保护身体免受疾病侵害至关重要。大多数关于免疫反应的研究都是在人类和小鼠等动物模型中进行的。然而，了解农场动物的免疫系统如何运作非常重要。鸡就是一个重要的例子：鸡是地球上最受欢迎的食用动物，每年孵化和饲养的鸡数量超过 500 亿只。就经济成本和动物福利而言，疾病控制是养鸡生产的主要挑战。另一个因素是一些鸟类疾病，例如禽流感，可能会感染人类，因此对人类健康构成重大挑战。在食品安全、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了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有很大不同。哺乳动物中专门负责免疫功能的一些器官，例如淋巴结，在鸟类中不存在，而鸟类有自己的专门免疫器官，而哺乳动物中不存在这些器官。哺乳动物和鸟类之间的一些免疫细胞是相似的，但尚不清楚它们是否具有相同的功能或对产生有效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。这些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。单核吞噬细胞的一项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，然后免疫系统的其他细胞可以做出适当的反应。从这个意义上说，它们向免疫系统的其余部分传达有关潜在病原体性质的信息。关于鸟类中哪些细胞类型呈现抗原的信息非常少。我们需要获得有关这些过程的更多信息，我们开发了一种新工具来识别和研究这些细胞，并且最近识别了一种非常重要的单核吞噬细胞类型，称为传统或经典树突细胞。这非常重要，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。本研究计划的主要目标是（1）鉴定不同年龄和不同组织的鸡传统树突状细胞并进行功能表征（2）产生缺乏这些传统树突状细胞的基因编辑鸡，以分离其特定功能（3）使用目标1中生成的基因编辑鸡来测试它们对抵抗细菌病原体沙门氏菌的重要性。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，从而提高生产成本、生物安全和生产鸡的福利

项目成果

Visualisation and characterisation of mononuclear phagocytes in the chicken respiratory tract using CSF1R-transgenic chickens.

• DOI: 10.1186/s13567-018-0598-7
• 发表时间: 2018-10-10
• 期刊: Veterinary research
• 影响因子: 4.4
• 作者: Sutton K;Costa T;Alber A;Bryson K;Borowska D;Balic A;Kaiser P;Stevens M;Vervelde L
• 通讯作者: Vervelde L

Antigen Sampling CSF1R-Expressing Epithelial Cells Are the Functional Equivalents of Mammalian M Cells in the Avian Follicle-Associated Epithelium

• DOI: 10.3389/fimmu.2019.02495
• 发表时间: 2019-10-22
• 期刊: FRONTIERS IN IMMUNOLOGY
• 影响因子: 7.3
• 作者: Balic, Adam;Chintoan-Uta, Cosmin;Vervelde, Lonneke
• 通讯作者: Vervelde, Lonneke

Regulation and function of macrophage colony-stimulating factor (CSF1) in the chicken immune system.

鸡免疫系统中巨噬细胞集落刺激因子（CSF1）的调节和功能。

• DOI: 10.1016/j.dci.2019.103586
• 发表时间: 2020
• 期刊: Developmental and comparative immunology
• 影响因子: 2.9
• 作者: Wu Z

Development of novel reagents to chicken FLT3, XCR1 and CSF2R for the identification and characterization of avian conventional dendritic cells.

• DOI: 10.1111/imm.13426
• 发表时间: 2022-02
• 期刊: IMMUNOLOGY
• 影响因子: 6.4
• 作者: Wu, Zhiguang;Hu, Tuanjun;Chintoan-Uta, Cosmin;Macdonald, Joni;Stevens, Mark P.;Sang, Helen;Hume, David A.;Kaiser, Pete;Balic, Adam
• 通讯作者: Balic, Adam