Defining the roles of TNF, lymphotoxin alpha and LIGHT in experimental visceral leishmaniasis

定义 TNF、α 淋巴毒素和 LIGHT 在实验性内脏利什曼病中的作用

• 批准号: nhmrc : 389850
• 负责人: Dr Christian Engwerda
• 金额: $ 27.35万
• 依托单位: Queensland Institute of Medical Research
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/defining-roles-tnf-visceral-leishmaniasis/97010
• 关键词: Defining; roles; TNF; lymphotoxin; alpha

Visceral leishmaniasis (VL) is an important human disease caused by the protozoan parasites Leishmania donovani and L. infantum (chagasi). Studies in experimental VL caused by L. donovani infection of mice have resulted in major insights into the causes of VL and the reasons why VL patients become severely immunocompromised. Work from our laboratory has shown that members of the TNF family of cytokines play key roles in the generation of effective immune responses during VL, but also mediate significant tissue pathology, particularly in the spleen, following L. donovani infection. In this grant, we will define the roles of several key members of the TNF family in the generation of immunity and pathology during experimental VL. We will also test if the activity of these molecules can be modulated to control disease without detrimental side effects. Results from this research have implication for the design of new vaccines and therapeutics to control VL. In addition, given the important role of TNF family members in cancers and autoimmune diseases, the work in this grant will have advance our understanding of pathogenic processes that are common to many important human diseases.

内脏利什曼病（VL）是一种重要的人类疾病，由原生动物寄生虫杜氏利什曼原虫和婴儿利什曼原虫（恰加西）引起。对小鼠杜氏乳杆菌感染引起的实验性 VL 的研究使人们对 VL 的原因以及 VL 患者出现严重免疫功能低下的原因有了深入的了解。我们实验室的工作表明，TNF 细胞因子家族成员在 VL 期间有效免疫反应的产生中发挥着关键作用，而且在杜氏乳杆菌感染后也介导重要的组织病理学，特别是在脾脏中。在这笔资助中，我们将定义 TNF 家族的几个关键成员在实验 VL 期间免疫和病理产生中的作用。我们还将测试是否可以调节这些分子的活性来控制疾病而不产生有害的副作用。这项研究的结果对于设计新的疫苗和治疗方法来控制 VL 具有重要意义。此外，鉴于 TNF 家族成员在癌症和自身免疫性疾病中的重要作用，这项资助的工作将增进我们对许多重要人类疾病常见的致病过程的理解。