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

内脏利什曼病是由杜氏利什曼原虫和利什曼原虫引起的人类重要疾病。infantum（chagasi）. L.引起实验性VL的研究donovani感染小鼠的研究已经导致了对VL的原因和VL患者变得严重免疫功能低下的原因的重大见解。我们实验室的工作已经表明，细胞因子的TNF家族的成员在VL期间有效免疫应答的产生中起关键作用，但也介导显著的组织病理学，特别是在L. Donovani感染在这项研究中，我们将确定TNF家族的几个关键成员在实验性VL过程中免疫和病理学的产生中的作用。我们还将测试这些分子的活性是否可以被调节以控制疾病而没有有害的副作用。这项研究的结果对设计新的疫苗和治疗方法来控制VL具有意义。此外，鉴于肿瘤坏死因子家族成员在癌症和自身免疫性疾病中的重要作用，这项资助的工作将促进我们对许多重要人类疾病常见的致病过程的理解。

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.