Innate immune sensing of viral DNA by avian macrophages

禽类巨噬细胞对病毒 DNA 的先天免疫感应

• 批准号: BB/S001336/1
• 负责人: Brian Ferguson
• 金额: $ 71.15万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FS001336%2F1
• 关键词: Innate; immune; sensing; viral; DNA

Chickens are a globally important food source and hence require protection from infectious diseases. The poultry industry in the UK alone is responsible for the production of more than one million tonnes of chicken meat and billions of eggs every year for consumption. This vast scale of farming necessitates that we understand which diseases pose a threat to the health of these chickens and how we can counter those threats. The use of vaccines is one a primary method used to help protect chickens from infections such as Newcastle disease, infectious bronchitis, fowlpox and Marek's disease. In order to effectively improve current vaccines or design new ones against emerging and zoonotic infections it is important to understand the fundamental mechanisms by which the chicken immune system works and how it interacts with pathogens. Such studies can lead not only to improvements in vaccine design but also to a greater understanding of immunology and virology as a whole. Indeed, the study of avian immunology and virology has lead to several important advances in both fields. In this study we aim to advance our understanding of how chicken cells detect the presence of DNA in the wrong place inside the cell. Such a mis-localisation can be a sign of infection or damage that triggers an alarm called the innate immune system to send signals into the infected or damaged tissue that something is wrong. This system is critical to fight off infections and to drive vaccination responses so understanding how it works will help in the fight against diseases such as Marek's that affect global chicken populations.

鸡是全球重要的食物来源，因此需要防止传染病。仅英国的家禽业每年就生产超过100万吨鸡肉和数十亿个鸡蛋供消费。这种大规模的养殖需要我们了解哪些疾病对这些鸡的健康构成威胁，以及我们如何应对这些威胁。使用疫苗是一种主要的方法，用于帮助保护鸡免受感染，如纽卡斯尔病，传染性支气管炎，鸡痘和马立克氏病。为了有效地改进现有的疫苗或设计新的疫苗来对抗新发和人畜共患感染，重要的是要了解鸡免疫系统工作的基本机制以及它如何与病原体相互作用。这些研究不仅可以改进疫苗设计，而且可以更好地理解整个免疫学和病毒学。事实上，鸟类免疫学和病毒学的研究已经在这两个领域取得了一些重要进展。在这项研究中，我们的目标是进一步了解鸡细胞如何检测细胞内错误位置的DNA。这样的错误定位可能是感染或损伤的迹象，它会触发一种称为先天免疫系统的警报，向感染或受损的组织发送信号，说明有什么不对劲。该系统对于抵御感染和推动疫苗接种反应至关重要，因此了解其工作原理将有助于对抗影响全球鸡群的马立克氏病等疾病。

项目成果

Chicken cGAS senses fowlpox virus infection and regulates macrophage effector functions

鸡cGAS感知鸡痘病毒感染并调节巨噬细胞效应功能

• DOI: 10.1101/2020.10.01.321422
• 发表时间: 2020
• 作者: Oliveira M

Vaccinia Virus Infection Inhibits Skin Dendritic Cell Migration to the Draining Lymph Node.

• DOI: 10.4049/jimmunol.2000928
• 发表时间: 2021-02-15
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Aggio JB;Krmeská V;Ferguson BJ;Wowk PF;Rothfuchs AG
• 通讯作者: Rothfuchs AG

Vaccinia Virus Infection Inhibits Skin Dendritic Cell Migration to Draining Lymph Node

痘苗病毒感染抑制皮肤树突状细胞迁移至引流淋巴结

• DOI: 10.17863/cam.92727
• 发表时间: 2021
• 作者: Ferguson B

DNA-PKcs is required for cGAS/STING-dependent viral DNA sensing in human cells.

DNA-PKcs 是人类细胞中 cGAS/STING 依赖性病毒 DNA 传感所必需的。

• DOI: 10.17863/cam.104643
• 发表时间: 2024
• 作者: Hristova D

Chicken cGAS Senses Fowlpox Virus Infection and Regulates Macrophage Effector Functions.

• DOI: 10.3389/fimmu.2020.613079
• 发表时间: 2020
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Oliveira M;Rodrigues DR;Guillory V;Kut E;Giotis ES;Skinner MA;Guabiraba R;Bryant CE;Ferguson BJ
• 通讯作者: Ferguson BJ