Leishmania Antigen Presentation by Infected Cells

描述（由申请人提供）：利什曼病是一种重要的人类和动物疾病，在世界范围内分布，包括在北美，最近报告了野狗的内源性传播。该病表现为一系列的表现，可累及皮肤和多个内脏器官。它是慢性的，并表现出自发缓解的趋势。这些寄生虫感染的免疫学研究提供了有价值的见解功能性T细胞发育应答抗原活化。然而，令人感兴趣的是，即使宿主对寄生虫产生强烈的免疫反应，利什曼原虫仍在被感染的宿主体内持续存在。这表明寄生虫已经进化出一种逃避免疫检测的策略。本研究表明，利什曼原虫会损害被感染巨噬细胞处理和向CD4+ T细胞呈递寄生虫分子的能力。阐明这一过程的潜在机制的方法建立在吞噬受体作为L. mexicana模型发病机制的决定因素的观察基础上。具体来说，研究确定了寄生虫通过Fc或补体受体内化时寄生物液泡内容物的进化。当液泡允许抗原呈递时，存在的主要液泡特征应该很容易辨别。这些研究将揭示可用于控制利什曼原虫的寄生虫过程

DESCRIPTION (provided by the applicant): Leishmaniasis is an important human and animal disease with a worldwide distribution including in North America where endogenous transmission in wild dogs has recently been reported. The disease presents as a spectrum of manifestations that can involve the skin and multiple visceral organs. It is chronic and exhibits a tendency for spontaneous remission. Immunological studies of infections by these parasites have provided valuable insights into functional T cell development in response to antigen activation. It is however intriguing that even though vigorous host immune responses are elicited in response to the parasite, Leishmania persist in the infected host. This suggests that the parasites have evolved a strategy to evade immune detection. This study proposes that Leishmania amastigotes impair the ability of infected macrophages to process and present parasite molecules to CD4+ T cells. The approach to elucidate the underlying mechanism of this process builds on observations that implicated the phagocytic receptor as a determinant of pathogenesis in the L. mexicana model. Specifically, studies ascertain the evolution of the contents of the parasitophorous vacuole when parasites are internalized through the Fc or complement receptors. The prevailing vacuole characteristics that exist when the vacuole is permissive of antigen presentation should be readily discerned. These studies will expose parasite processes that can be targeted for the control of Leishmania