INTERLEUKIN-2 INDUCED ANTIFUNGAL ACTIVITY

描述(改编自申请人的摘要)： 普通和特别是白色念珠菌感染是重要的原因 免疫受损个体的发病率和死亡率。本研究 将评估一种新的抗真菌机制，淋巴细胞直接通过 与白色念珠菌相互作用并影响它们。淋巴细胞在宿主中的作用 人们一直认为，预防真菌感染主要是通过 对吞噬细胞产生作用的细胞因子的阐述 人口。最近，淋巴细胞被证明可以相互作用。 直接与真菌结合，并发挥抗真菌作用。它的目的是 这项研究描绘了淋巴细胞黏附的过程， 被菌丝激活，并对菌丝和 白色念珠菌的酵母形态。本项目的具体目标是：1) 测定淋巴细胞与白念珠菌菌丝黏附的方式 酵母。2)确定和激活淋巴细胞的过程 由白色念珠菌菌丝引入进行胞质颗粒胞吐 还有酵母。3)测定淋巴细胞和淋巴细胞的抗真菌作用 白色念珠菌上的细胞质颗粒。这项研究是及时的，因为 免疫受损的人数在#年急剧增加 最近几年。免疫功能受损的人患真菌的风险最高 感染是：癌症患者；接受器官移植的患者 移植；糖尿病患者；长期接受皮质类固醇治疗的患者； 有医院获得性感染风险；以及有获得性免疫力的人 虚证。可归因性死亡率很高，因为 日益严重的真菌病。白色念珠菌有一种神秘的表现 不仅难于诊断，而且难于治疗。一直以来 很难理解哺乳动物寄主处理C. 白念珠菌。淋巴细胞可能通过以下途径提供重要的宿主防御机制 用来限制白色念珠菌。这种形式的抗真菌防御可能会成为 当主机防御机制中断时很重要。这项研究将 建立淋巴细胞的细胞和分子机制 直接与白色念珠菌相互作用并抑制其生长。澄清 这些机制将准确地描述一种替代方案，到目前为止 未描述的淋巴细胞可用于保护宿主免受感染的方式 真菌。这种精确的描述将影响越来越多的数字 由于免疫妥协而受到真菌疾病困扰的个人。 这项工作的重点是白色念珠菌，但对这些 细胞和分子机制应该在很大程度上促进 对淋巴细胞与其他细胞的相互作用及其生长抑制的认识 临床上也有重要的真菌。这项调查是一项重要的 了解寄主保护过程中的实验环节 对机会性微生物病原体的反应。因此，它将提供 关于一种新的、可能是重要的保护手段的信息 免疫功能受损的个人，避免临床相关的真菌感染。

DESCRIPTION (Adapted from the applicant's abstract): Fungal infections in general and Candida albicans infections in particular are important causes of morbidity and mortality in immunocompromised individuals. This study will evaluate a novel antifungal mechanism by which lymphocytes directly interact with and affect C. albicans. The role of lymphocytes in host protection from fungal infection has been thought to be primarily the elaboration of cytokines that produce effects upon phagocytic cell populations. More recently, lymphocytes have been demonstrated to interact directly with fungi and to exert an antifungal effect. It is the purpose of this investigation to delineate the process by which lymphocytes adhere to, are activated by, and produce an antifungal effect against the hyphal and yeast forms of C. albicans. The specific aims of this project are: 1) Determine the means by which lymphocytes adhere to C. albicans hyphae and yeast. 2) Identify the process by which lymphocytes are activated by and introduced to undergo cytoplasmic granule exocytosis by C. albicans hyphae and yeast. 3) Determine the antifungal effect of lymphocytes and lymphocyte cytoplasmic granules on C. albicans. This study is timely in that the numbers of immunocompromised individuals has dramatically increased in recent years. Immunocompromised individuals at greatest risk for fungal infections are: patients with cancer; those undergoing organ transplantation; diabetics; those on long-term corticosteroid therapy; those at risk for hospital acquired infection; and those with the acquired immune deficiency syndrome. Attributable mortality is high with the emergence of increasingly severe fungal disease. C. albicans has an occult presentation and is not only difficult to diagnose but also to treat. It has been difficult to understand the means by which the mammalian host deals with C. albicans. Lymphocytes may provide an important host defense mechanism by which to limit C. albicans. Such a form of antifungal defense may become important when host defense mechanisms are disrupted. This study will establish the cellular and molecular mechanisms by which lymphocytes directly interact with and inhibit the growth of C. albicans. Elucidation of these mechanisms will precisely describe an alternative, and as yet undescribed means by which lymphocytes may serve to protect the host from fungi. This precise description will impact the increasingly large numbers of individuals who, due to immunocompromise, are beset by fungal disease. The focus of this work is upon C. albicans, but the elucidation of these cellular and molecular mechanisms should contribute significantly to the understanding of lymphocyte interactions with and growth inhibition of other clinically important fungi as well. This investigation is an important experimental link in the process of understanding the host protective response to opportunistic microbial pathogens. As such it will provide information about a new and possibly important means by which to protect immunocompromised individuals from clinically relevant fungal infection.