FUNGAL ANTIGENS AND ANTIFUNGAL RESPONSE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 常见霉菌烟曲霉是一种条件致病菌，也是侵袭性曲霉病最常见的病原体。这种疾病通常是由免疫功能低下的宿主感染的，包括癌症患者，据报道死亡率为80%。我们的长期目标是开发一种疫苗，并为曲霉病的早期诊断和监测提供更好的手段。我们的具体假设是：1)某些曲霉抗原具有免疫保护作用，2)某些抗原可以作为曲霉感染早期阶段的指标。我们的假设基于以下观察结果。首先，接种真菌粗蛋白提取物或活分生孢子的小鼠在免疫抑制后存活(例如，使用皮质类固醇治疗)。其次，这种真菌在其生命周期的不同阶段积极分泌各种特定的蛋白质和多肽。曲霉菌的60多种抗原和过敏原已被描述(1-4)。然而，其中只有一种，半乳甘露聚糖，被常规检测来诊断曲霉感染。基于这些观察，我们的实验重点是烟曲霉菌抗原的鉴定、结构和免疫学特征。我们计划利用和改进新的质谱学技术，从培养上清液、支气管肺泡灌洗液(BAL)、血液和尿液等复杂混合物中检测和鉴定真菌来源的蛋白质和多肽。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The common mold, Aspergillus fumigatus, is an opportunistic pathogen and the most frequently isolated causative agent of invasive aspergillosis. The disease is often contracted by immunocompromised hosts, including cancer patients, with reported mortality rates > 80%. Our long-term goals are to develop a vaccine and to provide better means for the early diagnosis and monitoring of aspergillosis. Our specific hypotheses are: 1) certain aspergillus antigens have an immunoprotective effect, and 2) some antigens may serve as indicators of early stages of aspergillus infections. We base our hypotheses on the following observations. First, mice vaccinated with crude fungal protein extracts or viable conidia survive infection following immunosuppression (e.g., with corticosteroid treatment). Second, the fungus actively secretes a variety of specific proteins and peptides at different stages of its lifecycle. More than 60 antigens and allergens of Aspergillus have been described (1-4). However, only one of them, the polysaccharide galactomannan, is routinely assayed to diagnose Aspergillus infections. Based on these observations, our experimental focus is on the identification and structural and immunological characterization of A. fumigatus antigens. We plan to utilize and improve novel mass spectrometric techniques to detect and identify proteins and peptides of fungal origin from complex mixtures such as culture supernatants, bronchoalveolar lavage (BAL) fluid, blood and urine.