INTERLEUKIN-2 INDUCED ANTI-FUNGAL ACTIVITY

INTERLEUKIN-2 诱导的抗真菌活性

• 批准号: 3146154
• 负责人: HERBERT L. MATHEWS
• 金额: $ 16.87万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-03-01 至 1995-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3146154
• 关键词: Candida albicans; antifungal agents; cellular immunity; flow cytometry; host organism interaction; interleukin 2; laboratory mouse; leukocyte activation /transformation; lymphocyte; microorganism growth; microorganism immunology; mycosis; tissue /cell culture

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 means by which to limit the development of fungal infections caused by Candida albicans. It has been very difficult to understand the means by which the mammalian host deals with limiting the growth of fungal hyphae, that reach lengths of 40-60 um, in vivo. Activated lymphocytes may influence the growth of fungal hyphae. If true, then such activated lymphocytes may provide an important host defense mechanism by which fungi may be limited. Such a form of anti-fungal defense may be important when normal host defense mechanisms are disrupted or as an adjunct to other anti-fungal mechanisms in the normal host. It is the purpose of this investigation to clearly identify the immunological nature and the functional activity of such an activated lymphocyte population. This identification will permit a direct assessment of the potential biological activity of the activated lymphocyte population and will lead to a clearer understanding of the mammalian host protective response to Candida, albicans. These observations are important since during the last two decades the incidence of fungal infections in general and Candida albicans infections in particular have increased markedly. Hematogenously disseminated Candida albicans infections have become increasingly significant in patients with; solid tumors, hematological malignancies, solid organ transplants, and in patients undergoing chemotherapy and in intensive care units. Candida albicans attributable mortality is high with the emergence of increasingly severe fungal diseases. Candida albicans has an occult presentation and is not only difficult to diagnose but are also difficult to treat. This investigation will determine whether interleukin-2 activated lymphocytes participate in and correlate with enhanced anti-fungal activity. The objectives of this project are to; 1) determine optimal growth and culture conditions for the interleukin-2 induction of maximal anti-fungal activity, 2) identify the functional and phenotypic characteristic of the anti-fungal lymphocytes, 3) clarify the mechanism of anti-fungal activity and 4) determine the effect of interleukin-2 induced lymphocytes on the survival rate of mice with experimental Candida albicans infections. This investigation will serve as an important experimental step in the analysis of the host protective response to the hyphal form of Candida albicans and will lead to a more complete understanding of the role of lymphocytes in the protection of immunocompromised individuals infected with fungi.

真菌感染，尤其是白色念珠菌感染 是免疫低下患者发病和死亡的重要原因吗？ 个人。这项研究将评估一种新的方法，通过它来限制 由白色念珠菌引起的真菌感染的发展。一直以来 很难理解哺乳动物寄主交易的方式 通过限制长达40-60微米的真菌菌丝的生长， 在活体内。活化的淋巴细胞可能影响真菌菌丝的生长。 如果是真的，那么这种被激活的淋巴细胞可能会提供一个重要的宿主 真菌可能受到限制的防御机制。这样一种形式的 当正常的寄主防御机制时，抗真菌防御可能是重要的 被破坏或作为其他抗真菌机制的附属物 普通主机。这次调查的目的是清楚地确定 这种活性物质的免疫学性质和功能活性 淋巴细胞群。这一鉴定将允许直接评估 激活的淋巴细胞群体的潜在生物学活性 这将使我们更清楚地了解哺乳动物的宿主保护 对念珠菌、白念珠菌的反应。这些观察结果很重要，因为 在过去的二十年里，真菌感染的发病率总体上 尤其是白色念珠菌的感染明显增加。 经血液传播的白色念珠菌感染已成为 在实体瘤、血液病患者中的意义越来越大 恶性肿瘤，实体器官移植，以及在接受 化疗和重症监护病房。可归因于白色念珠菌 随着越来越严重的真菌的出现，死亡率很高 疾病。白色念珠菌有一种神秘的表现，不仅 难以诊断，但也难以治疗。这项调查 将决定白细胞介素2激活的淋巴细胞是否参与 并与增强的抗真菌活性相关。这样做的目的是 项目的目的是：1)确定最适宜的生长和培养条件 白介素2诱导最大抗真菌活性，2)鉴定 抗真菌淋巴细胞的功能和表型特征 阐明其抗真菌作用的机制；4)测定其抗真菌作用 白介素2诱导的淋巴细胞对小鼠存活率的影响 实验性白色念珠菌感染。这项调查将作为 分析寄主保护的一个重要实验步骤 对菌丝形态的白色念珠菌的反应将导致更多 对淋巴细胞在免疫保护中的作用的全面认识 感染真菌的免疫功能受损的个体。