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

肠道沙门氏菌在许多动物中引起广泛的疾病。沙门氏菌感染给养殖业造成的经济损失可能非常高，但同样重要的是，许多感染动物的血清型也会导致人类食物中毒和肠胃炎。在小鼠中，感染肠沙门氏菌血清型鼠伤寒沙门氏菌（S. Typhimurium）引起的临床症状与人类和鸡的侵袭性感染非常相似。因此，对小鼠的感染研究将使我们了解感染如何可能在其他动物物种中发展和传播。为动物接种疫苗以降低肉和蛋中的沙门氏菌水平，将减少感染传播给人类的机会。小鼠感染模型也非常适合研究疫苗。一种成功的疫苗必须能产生强烈的免疫反应，而且必须对年轻人和老年人都是安全的。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是至关重要的。这种动物通过一种叫做模式识别受体（PRRs）的特殊蛋白质来检测这些细菌分子的存在，然后启动宿主防御机制来清除感染。这些受体也被认为在产生对疫苗的良好反应方面很重要，但目前尚不清楚这是如何发生的。例如，关于鸡是否使用PRRs来控制沙门氏菌感染的知识了解得太少，无法在这个物种中进行这些研究，但是我们可以使用没有PRRs的小鼠来确定这些蛋白质对控制和预防沙门氏菌是否重要。在这里，我们将确定哪些PRRs在保护小鼠免受沙门氏菌感染方面很重要。这项工作的影响将是确定哪些PRRs在产生针对沙门氏菌的成功保护性免疫反应方面是重要的，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。

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.