INTERLEUKIN-2 INDUCED ANTIFUNGAL ACTIVITY

描述（改编自申请人摘要）： 一般和白色念珠菌感染，特别是重要的原因 发病率和死亡率。 本研究 将评估一种新的抗真菌机制， 与C相互作用并影响C。白色念珠菌 淋巴细胞在宿主中的作用 保护免受真菌感染被认为主要是 对吞噬细胞产生作用的细胞因子的制备 人口数量。 最近，淋巴细胞已被证明可以相互作用， 直接与真菌接触并发挥抗真菌作用。 才是目的 这项研究描绘了淋巴细胞粘附的过程， 被菌丝激活并产生抗真菌作用， 酵母型C.白色念珠菌 该项目的具体目标是：1） 确定淋巴细胞粘附于C的方式。白色念珠菌菌丝和 酵母 2)识别淋巴细胞被激活的过程， 被C.白色念珠菌菌丝 和酵母。 3)测定淋巴细胞和淋巴细胞的抗真菌作用 C.白色念珠菌 这项研究是及时的，因为 免疫功能低下的人数急剧增加， 近年 免疫功能低下的人患真菌感染的风险最大 感染是：癌症患者;那些接受器官移植的人 移植;糖尿病;长期皮质类固醇治疗; 有医院获得性感染风险的人;以及具有获得性免疫的人 虚证 归因死亡率很高， 越来越严重的真菌病。 C.白色念珠菌具有隐匿性表现 不仅难以诊断，而且难以治疗。 很难理解哺乳动物宿主处理C. 白色念珠菌 淋巴细胞可能提供一个重要的宿主防御机制， 从而限制C。白色念珠菌 这种形式的抗真菌防御可能成为 当宿主防御机制被破坏时，这一点很重要。 本研究将 建立细胞和分子机制， 直接与C.白色念珠菌 阐发 这些机制将准确地描述一种替代方案，到目前为止， 淋巴细胞可能用于保护宿主免受 真菌 这种精确的描述将影响越来越多的数字， 由于免疫功能低下而被真菌疾病困扰的个体。 本工作的重点是C。白色念珠菌，但阐明这些 细胞和分子机制应有助于显着 了解淋巴细胞与其他细胞的相互作用和生长抑制 临床上重要的真菌。 这项调查是一项重要的 在实验环节中了解主机保护的过程 对机会性微生物病原体的反应。 因此，它将提供 关于一种新的和可能重要的保护手段的信息， 免疫功能低下的人从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.