Characterisation of the Pattern Recognition Receptors required for the development of protective immunity against Salmonella infection

沙门氏菌感染保护性免疫发展所需的模式识别受体的表征

• 批准号: BB/H003916/1
• 负责人: Clare Bryant
• 金额: $ 65.42万
• 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: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FH003916%2F1
• 关键词: Characterisation; Pattern; Recognition; Receptors; required

Salmonella enterica causes a wide range of diseases in many animals. Economic losses to the farming industry through Salmonella infection are potentially very high, but also important is the fact that a number of serovars that infect animals can also cause food poisoning and gastroenteritis in humans. In mice, infection with Salmonella enterica serovar Typhimurium (S. Typhimurium) causes clinical signs that are very similar to those seen in invasive infections of humans and chickens. Infection studies in mice will therefore allow us to understand how infection is likely to develop and spread within other species of animals. Vaccination of animals to lower the levels of Salmonella in meat and eggs will reduce the chances of infection spreading to people. The mouse model of infection is also excellent for studying vaccines. A successful vaccine must be generate a strong immune response but must also be safe for application in young and older individuals. Understanding how Salmonella interacts with its host to generate an immune response is critical when trying to design new vaccines. The animal detects the presence of these bacterial molecules through specialised proteins called Pattern Recognition Receptors (PRRs) which then initiate host defence mechanisms to clear the infection. These receptors are also believed to be important in generating a good response to vaccines, but precisely how this happens is currently unclear. The knowledge on whether chickens, for example, use PRRs to control Salmonella infection is too poorly understood to perform these studies in this species, but we can use mice without PRRs to determine whether these proteins are important for the control of, and protection against, Salmonella. Here we will determine which PRRs are important in protecting mice against Salmonella infections. The impact of this work will be to determine which PRRs are important in generating successful protective immune responses against Salmonella and these data will therefore allow us to design better vaccines for chickens, other domestic animals and humans.

肠沙门氏菌在许多动物中引起广泛的疾病。通过沙门氏菌感染给农业行业的经济损失可能很高，但同样重要的是，许多感染动物的血清射手也可能引起人类食物中毒和胃肠炎。在小鼠中，用肠肠孢子虫（S. typhimurium）感染了临床体征，与人类和鸡的侵入性感染非常相似。因此，在小鼠中的感染研究将使我们能够了解感染如何在其他动物中发展和传播。动物的疫苗接种以降低肉和鸡蛋中沙门氏菌的水平，将减少感染传播的机会。感染小鼠模型也非常适合研究疫苗。成功的疫苗必须产生强烈的免疫反应，但还必须安全地适用于年轻人和老年人。在尝试设计新疫苗时，了解沙门氏菌如何与宿主相互作用以产生免疫反应至关重要。该动物通过称为模式识别受体（PRR）的专门蛋白质检测到这些细菌分子的存在，然后启动宿主防御机制清除感染。人们还认为，这些受体在对疫苗的良好反应中很重要，但是目前尚不清楚这种情况的发生方式。例如，关于鸡是否使用PRR来控制沙门氏菌感染的知识对在该物种中进行这些研究的理解太差，但是我们可以使用无PRR的小鼠来确定这些蛋白质对控制和保护沙门氏菌是否重要。在这里，我们将确定哪些PRR对于保护小鼠免受沙门氏菌感染很重要。这项工作的影响将是确定哪些PRR对于对沙门氏菌的成功保护性免疫反应很重要，因此这些数据将使我们能够为鸡，其他家畜和人类设计更好的疫苗。

项目成果

The N-terminal loop of IRAK-4 death domain regulates ordered assembly of the Myddosome signalling scaffold

IRAK-4 死亡结构域的 N 端环调节 Myddosome 信号支架的有序组装

• DOI: 10.17863/cam.10185
• 发表时间: 2016
• 作者: Dossang A

Mice, men and the relatives: cross-species studies underpin innate immunity.

• DOI: 10.1098/rsob.120015
• 发表时间: 2012-04
• 期刊: Open biology
• 影响因子: 5.8
• 作者: Bryant CE;Monie TP
• 通讯作者: Monie TP

The COP II adaptor protein TMED7 is required to initiate and mediate the delivery of TLR4 to the plasma membrane.

• DOI: 10.1126/scisignal.2005275
• 发表时间: 2014-07-29
• 期刊: Science signaling
• 影响因子: 7.3
• 作者: Liaunardy-Jopeace A;Bryant CE;Gay NJ
• 通讯作者: Gay NJ

The N-terminal loop of IRAK-4 death domain regulates ordered assembly of the Myddosome signalling scaffold.

• DOI: 10.1038/srep37267
• 发表时间: 2016-11-23
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Dossang AC;Motshwene PG;Yang Y;Symmons MF;Bryant CE;Borman S;George J;Weber AN;Gay NJ
• 通讯作者: Gay NJ