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

基本信息

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

项目摘要

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

成人生物体的血液和组织由多种细胞类型组成，包括携带氧和免疫细胞的红细胞。免疫细胞对病毒或微生物的感染反应，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，例如疫苗接种，对免疫系统如何捍卫人体免受疾病的理解至关重要。关于免疫反应的大多数研究都是对人类和小鼠等动物模型进行的。但是，我们了解农场动物的免疫系统的工作原理非常重要。一个关键的例子是鸡肉：鸡是地球上最受欢迎的食物动物，每年孵化和饲养超过500亿。就经济成本和动物福利而言，控制疾病是鸡生产的主要挑战。另一个因素是，某些鸟类疾病（例如鸟类流感）可能会感染人类，因此是对人类健康的主要挑战。在粮食安全，公共卫生和消费者安全方面保护家禽行业至关重要，不仅在英国，而且在全球范围内。增加我们对鸡肉免疫系统的理解和对疾病的免疫反应的一个复杂因素是，鸟类的免疫系统与哺乳动物的免疫系统完全不同。一些专门用于哺乳动物的免疫功能的器官（例如淋巴结）不存在鸟类中，而鸟类则具有自己的专业免疫器官，这些器官在哺乳动物中不存在。哺乳动物和鸟类之间的某些免疫细胞相似，但是尚不清楚它们是否具有相同的功能或对有效免疫反应产生不同的要求。免疫细胞最重要的类型之一是单核吞噬细胞。这些是具有许多不同功能的一类细胞，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材料并将其呈现给免疫系统的其他细胞，然后可以做出适当的反应。从这个意义上讲，他们将有关潜在病原体的性质的信息传达给免疫系统的其余部分。关于鸟类中哪种细胞类型的抗原的信息很少。我们需要获取有关这些过程的更多信息，并开发了一种用于识别和研究这些细胞的新工具，并最近识别了一种非常重要的单核吞噬细胞，该吞噬细胞被称为常规或经典的树突状细胞。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。该研究提案的主要目标是（1）识别和在功能上表征鸡在不同年龄和不同组织中的鸟类传统的树突状细胞（2）产生缺乏这些常规的树突状细胞的基因编辑的鸟类，以隔离它们的特定功能（3），以使用目标1来测试对抗salmane salmane salmane salmane salmane salmane的重要性1的基因编辑的鸟类。从长远来看，这种知识帮助我们开发了更好的疫苗，以预防鸡的疾病，以提高生产成本，生物安全性和生产鸡的福利

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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

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

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。