Uncovering the divergent roles of type I and III Interferons in Salmonella infection

研究人员在60多年前发现，感染病毒的细胞会产生一种物质，保护邻近细胞免受病毒感染。这种分泌的物质被称为干扰素，因为它“干扰”感染。从那时起，许多不同的干扰素被发现，它们在抗病毒免疫中的功能得到了广泛的研究。干扰素甚至被用作对抗病毒感染的疗法。然而，目前还不清楚干扰素是否在细菌感染中具有类似的作用。细菌感染对人类健康构成重大威胁，并且有越来越多的细菌对几乎所有临床可用的抗生素具有耐药性。因此，我们必须发现细菌感染的替代治疗方法。一个有吸引力的研究领域是激活免疫系统以自然对抗感染的药物。干扰素就是这样一种候选的抗菌疗法，但我们首先需要更好地了解它们在细菌感染中的作用，部分是为了看看它们是否会产生有害影响。这项建议将集中在主要的人类病原体肠道沙门氏菌上，这种细菌每年影响超过1亿人，导致不同的疾病，包括胃肠炎和伤寒。沙门氏菌侵入人体细胞，在那里繁殖并躲避免疫系统。令人担忧的是，沙门氏菌的耐药菌株正在地球仪各地出现，使这种病原体成为人类健康的主要威胁。在这个建议中，我们将研究不同的干扰素家族是否在沙门氏菌感染中发挥有益或有害的作用。我们将研究干扰素如何影响沙门氏菌在宿主细胞内繁殖和控制免疫反应的能力。我们还将研究不同干扰素在沙门氏菌感染小鼠中的功能。该项目还将确定沙门氏菌用于致病的毒力蛋白是否可以改变细胞产生或响应干扰素的能力。总的来说，这项研究将使我们更好地了解干扰素在沙门氏菌感染中的功能，以及我们如何利用这些知识开发沙门氏菌感染的新疗法。

Researchers discovered more than 60 years ago that cells infected with viruses produce a substance that protects neighbouring cells from viral infection. This secreted substance was termed Interferon, as it 'interferes' with infection. Since then, many different interferons have been discovered, and their functions in anti-viral immunity have been extensively studied. Interferons has even been used as a therapy against viral infections. However, it remains unclear whether interferons have similar roles during bacterial infections. Bacterial infections pose a significant threat to human health and there are increasing numbers of bacteria that are resistant to almost all clinically available antibiotics. It is therefore essential that we discover alternative treatments for bacterial infections. An attractive area of research are drugs that activate the immune system to naturally combat infection. Interferons are one such candidate anti-bacterial therapy, but we first need a greater understanding of their roles in bacterial infection, in part to see if they could have harmful effects.This proposal will focus on the major human pathogen Salmonella enterica, a bacterium which affects over 100 million people each year, causing different diseases including gastroenteritis and typhoid fever. Salmonella invades human cells where they multiply and hide from the immune system. Worryingly, resistant strains of Salmonella are emerging across the globe, rendering this pathogen a major threat to human health. In this proposal, we will study whether different interferon families play beneficial or harmful roles in Salmonella infection. We will investigate how interferons affect the ability of Salmonella to multiply within host cells and control immune responses. We will also study the functions of different interferons in mice infected with Salmonella. This project will also identify if virulence proteins that Salmonella uses to cause disease can alter the ability of cells to produce or respond to interferon.Overall, this research will give us a better understanding of the functions of interferons in Salmonella infection, and how we can use this knowledge to develop new treatments for Salmonella infections.