Leishmania Antigen Presentation by Infected Cells

描述(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，包括最近在北美报告的野狗内源性传播。这种疾病表现为一系列表现，可累及皮肤和多个内脏器官。它是慢性的，有自发缓解的趋势。对这些寄生虫感染的免疫学研究为抗原激活后功能性T细胞的发育提供了有价值的见解。然而，有趣的是，即使对寄生虫的反应会引发强烈的宿主免疫反应，利什曼原虫仍会在受感染的宿主中持续存在。这表明寄生虫已经进化出一种逃避免疫检测的策略。这项研究表明，利什曼原虫的无鞭毛体损害了被感染的巨噬细胞处理寄生虫分子并将其呈递给CD4+T细胞的能力。阐明这一过程的潜在机制的方法建立在观察到吞噬细胞受体作为墨西哥乳杆菌模型致病的决定因素的基础上。具体地说，研究确定了当寄生虫通过Fc或补体受体内化时，寄生虫空泡内容的演变。当空泡允许抗原呈递时，普遍存在的空泡特征应该很容易辨别出来。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