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INTERLEUKIN-2 INDUCED ANTIFUNGAL ACTIVITY

INTERLEUKIN-2 诱导的抗真菌活性

基本信息

批准号：
2672056
负责人：
HERBERT L. MATHEWS
金额：
$ 17.61万
依托单位：
LOYOLA UNIVERSITY CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
1992
资助国家：
美国
起止时间：
1992-03-01 至 2000-07-31
项目状态：
已结题

项目摘要

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.

描述（改编自申请人的摘要）：真菌感染一般感染和白色念珠菌感染尤其是重要原因免疫功能低下个体的发病率和死亡率。这项研究将评估一种新的抗真菌机制，通过该机制淋巴细胞可以直接与白色念珠菌相互作用并对其产生影响。淋巴细胞在宿主体内的作用防止真菌感染被认为主要是对吞噬细胞产生影响的细胞因子的阐述人口。最近，淋巴细胞已被证明可以相互作用直接与真菌作用并发挥抗真菌作用。其目的是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白色念珠菌的酵母形式。该项目的具体目标是：1）确定淋巴细胞粘附到白色念珠菌菌丝的方式和酵母。 2) 确定淋巴细胞被和激活的过程被白色念珠菌菌丝引入细胞质颗粒胞吐作用和酵母。 3）测定淋巴细胞和淋巴细胞的抗真菌作用白色念珠菌的细胞质颗粒。这项研究是及时的，因为免疫功能低下者的数量急剧增加近年来。免疫功能低下的个体感染真菌的风险最大感染者是：癌症患者；那些接受器官移植的人移植；糖尿病患者；长期接受皮质类固醇治疗的患者；那些有医院获得性感染的风险；以及那些具有获得性免疫的人缺乏综合症。随着疾病的出现，归因死亡率很高日益严重的真菌病害。白色念珠菌具有神秘的表现不仅诊断困难，而且治疗也困难。它一直很难理解哺乳动物宿主处理 C 的方式。白色念珠菌。淋巴细胞可能通过以下方式提供重要的宿主防御机制：用于限制白色念珠菌。这种形式的抗真菌防御可能会成为当宿主防御机制被破坏时很重要。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。说明这些机制将精确地描述一种替代方案，并且到目前为止淋巴细胞可以用来保护宿主免受感染的未描述的方法真菌。这种精确的描述将影响越来越大的数字由于免疫功能低下而受到真菌病困扰的个体。这项工作的重点是白色念珠菌，但这些的阐明细胞和分子机制应该对了解淋巴细胞与其他细胞的相互作用和生长抑制也是临床上重要的真菌。此次调查具有重要意义了解宿主防护过程中的实验环节对机会性微生物病原体的反应。因此它将提供有关新的且可能重要的保护手段的信息因临床相关真菌感染而导致免疫功能低下的个体。