Immunology and Immunopathology of visceral leishmaniasis

内脏利什曼病的免疫学和免疫病理学

• 批准号: G1000230-E01/1
• 负责人: Paul Kaye
• 金额: $ 241.61万
• 依托单位: University of York
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1000230-E01%2F1
• 关键词: Immunology; Immunopathology; visceral; leishmaniasis

Leishmaniasis is a disease caused when people are bitten by sandflies that contain a small single cell parasite, called Leishmania. Although some people never get sick, many develop local skin ulcers or a potentially fatal disease that affects the internal organs, called visceral leishmaniasis (kala azar or ?black sickness?). Why different people get different types of disease is not known, but it may relate to the type of Leishmania they are infected with and their health of their immune system. 2 million people get leishmaniasis every year (in 88 countries, including some in Europe) and visceral leishmaniasis is responsible for over 60,000 deaths annually. As the parasites live deep in the tissues (spleen, liver, bone marrow), it is difficult in sick people to see exactly how they are affecting our immune system and to find ways to improve how the immune system deals with them. Therefore, we need to use experimental models of the disease to study these questions. Although much progress has been made, experimental models cannot provide the whole picture and there may be important differences in how mice and people respond to these parasites, or in how much damage the immune system does to our organs trying to fight the infection. We wish to conduct an integrated research programme to let us study disease processes in human and mouse tissues side by side. This approach is important, both to see whether the responses in mice also occur in man (thus supporting clinical study of drugs/vaccines developed in mice) and conversely to see whether we can improve the predictive nature of models used for testing drugs/vaccines. We will be studying how Leishmania is eaten by white blood cells (phagocytes) in the liver, and how the expression of our genes changes in response to the infection. We will develop new microscopy approaches that allow us to see how infection affects phagocyte function and their ability to coordinate inflammation. We will use tissues samples taken from people during treatment and also at post mortem, to observe how well their immune systems have responded to treatment or to understand what went wrong that led to their death. In combination, these studies will provide much important new information on human disease, and help to reduce and improve the quality of animal experimentation.

利什曼病是一种疾病，当人们被含有小单细胞寄生虫（称为利什曼原虫）的沙叶咬伤时引起的疾病。尽管有些人从未生病，但许多人会出现当地的皮肤溃疡或可能影响内部器官的潜在致命疾病，称为内脏利什曼病（Kala Azar或？黑人疾病？）。为什么不同的人会发现不同类型的疾病，但它可能与他们感染的利什曼尼亚类型以及免疫系统的健康有关。每年有200万人患利什曼病（在88个国家，包括欧洲的一些国家）和内脏利什曼病，每年造成60,000多人死亡。由于寄生虫生活在组织深处（脾脏，肝脏，骨髓）时，病人很难确切地看到它们如何影响我们的免疫系统，并找到改善免疫系统如何处理它们的方法。因此，我们需要使用疾病的实验模型来研究这些问题。尽管取得了很大的进展，但实验模型无法提供整个情况，并且在小鼠和人们对这些寄生虫的反应方式，或免疫系统对试图对抗感染作斗争的器官造成的损害的程度可能存在重要差异。我们希望开展一项综合研究计划，让我们并排研究人类和小鼠组织中的疾病过程。这种方法很重要，既要查看小鼠的反应是否也出现在人中（因此支持小鼠中开发的药物/疫苗的临床研究），并且相反，以查看我们是否可以改善用于测试药物/疫苗的模型的预测性。我们将研究肝脏中的白细胞（吞噬细胞）如何食用利什曼原虫，以及我们基因的表达如何反应感染。我们将开发新的显微镜方法，使我们能够了解感染如何影响吞噬细胞功能及其协调炎症的能力。我们将在治疗期间和验尸中使用从人中采集的组织样本，以观察其免疫系统对治疗的反应程度或了解导致其死亡的问题。结合起来，这些研究将为人类疾病提供许多重要的新信息，并有助于降低和改善动物实验的质量。