Engineering Galleria Mellonella as a model for infection, immunity and inflammation

工程大蜡螟作为感染、免疫和炎症的模型

• 批准号: NC/T001518/1
• 负责人: James Wakefield
• 金额: $ 49.25万
• 依托单位: UNIVERSITY OF EXETER
• 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=NC%2FT001518%2F1
• 关键词: Engineering; Galleria; Mellonella; model; infection

Growing evidence supports the use of the larvae of the waxmoth, Galleria Mellonella, as an in vivo animal partial replacement model, particularly in the related fields of infection, immunity and inflammation. Although they are insects, their immune system is very similar to humans. There is huge potential impact on the number of rodents used in scientific research, if Galleria can be optimised as a model organism. However, currently, the health of larvae after injection with bacteria or fungal pathogens is monitored only by a crude assessment of whether/when they turn black and die. In the first part of this project, we will make transgenic larvae that glow (fluoresce) differentially under stress, infection, immune challenge or inflammatory status. We will light up their macrophages, the cells in the immune system that wander around, looking for foreign pathogens and "eating them". This will allow us to measure the movement of this important type of cell before and after infection, revolutionising the amount and type of information we can obtain about the way animals, and we, respond to infection.The second aim of the project is to use these fluorescent Galleria larvae to understand how the most common cause of human fungal disease in the world, a pathogen called Candida albicans, hides itself from our immune system. We know that Candida has something on their cell surface that the immune system normally recognises but that, in some cases, their environment triggers a change that ends up masking this signal. We will expose Candida to many of these sorts of environments and ask how effective the glowing Galleria macrophages are at recognising the fungus. Our work will therefore not only figure out the key molecular signals that mask Candida from the immune system, potentially identifying candidate molecules for new anti-fungal agents, but also has the potential to revolutionise the use of Galleria as mouse replacement model, saving many thousands of mice from being used in scientific research in the future.

越来越多的证据支持使用蜡螟的幼虫，Galleria Mellonella，作为体内动物部分替代模型，特别是在感染，免疫和炎症的相关领域。虽然它们是昆虫，但它们的免疫系统与人类非常相似。如果Galleria可以作为一种模式生物进行优化，那么在科学研究中使用的啮齿动物数量将受到巨大的潜在影响。然而，目前，在注射细菌或真菌病原体后，仅通过粗略评估它们是否/何时变黑和死亡来监测幼虫的健康。在这个项目的第一部分，我们将使转基因幼虫在压力，感染，免疫挑战或炎症状态下发光（荧光）差异。我们将点亮他们的巨噬细胞，这些细胞在免疫系统中四处游荡，寻找外来病原体并“吃掉它们”。这将使我们能够测量这种重要类型的细胞在感染前后的运动，彻底改变我们可以获得的关于动物和我们对感染的反应方式的信息的数量和类型。该项目的第二个目的是使用这些荧光Galleria幼虫来了解世界上最常见的人类真菌疾病的原因，一种称为白色念珠菌的病原体，隐藏在我们的免疫系统中我们知道念珠菌的细胞表面有一些免疫系统通常可以识别的东西，但在某些情况下，它们的环境引发了一种变化，最终掩盖了这种信号。我们将把念珠菌暴露在许多这样的环境中，并询问发光的Galleria巨噬细胞在识别真菌方面的有效性。因此，我们的工作不仅将找出从免疫系统中掩盖念珠菌的关键分子信号，可能识别新的抗真菌药物的候选分子，而且有可能彻底改变Galleria作为小鼠替代模型的使用，挽救成千上万的小鼠，使其在未来的科学研究中不再被使用。