MWF Mycobacteria antigens in occupational hypersensitivity pneumonitis

MWF 职业性过敏性肺炎中的分枝杆菌抗原

• 批准号: 8301478
• 负责人: Jagjit S Yadav
• 金额: $ 38.28万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8301478
• 关键词: MWF; Mycobacteria; antigens; occupational; hypersensitivity

Project summary Occupational hypersensitivity pneumonitis (HP) in machine workers has been associated with mycobacteria that frequently colonize modern water-based metalworking fluids (MWFs). HP is an immune-mediated lung disease caused by inhalation of microbial antigens and is relatively poorly studied in terms of its diagnosis, pathogenesis, and treatment. Overall goal of this study is to identify and characterize antigens associated with HP-inducing potential of MWF mycobacteria species M. immunogenum (MI) and M. chelonae (MC) and evaluate their potential for HP immunodiagnosis and exposure assessment. In previous funding cycles, we have isolated multiple strains (genotypes) of both the species with variable antigenic characteristics. We will test our hypothesis that antigen diversity in MWF mycobacteria strains prevalent in commercial MWF is responsible for differentially inducing the HP symptoms and underlying immune response, and that the responsible specific antigens could form the basis for more informative diagnosis and personal and environmental exposure assessment. The specific aims are to: (1). Identify key antigens in MI and MC strains based on their relative interaction with the host immune system in an optimized mouse model of HP; (2). Recombinant production of the identified key antigens by cloning and protein expression and generation of specific antibodies; (3). Investigate potential of the specific antigens for early personal exposure assessment and immunodiagnosis in symptomatic versus asymptomatic individuals; (4). Evaluate potential of the specific antigen(s) of MWF mycobacteria for environmental exposure assessment (fluid monitoring). Relative immunogenicity of the isolated different genotypes of MI (6) and MC (4) will be compared based on HP induction potential and cell-mediated immune response using our optimized mouse model and the putative protein antigens will be identified by differential immunoproteomic profiling. The recombinantly expressed antigens will be evaluated for their potential for immunodiagnosis using the mouse model and human subjects, particularly in terms of differentiation of the asymptomatic (exposed) versus symptomatic (HP patients) and for environmental exposure assessment. The resulting information will help NORA's objectives by providing a set of tools for mycobacterial exposure assessment and HP immunodiagnosis; these outcomes will facilitate future epidemiological studies and development of prevention (vaccination) and intervention strategies for MWF exposures in long-term.

项目概要 机械工人职业性过敏性肺炎（HP） 与经常在现代水基金属加工中定殖的分枝杆菌有关 流体（MWF）。 HP 是一种免疫介导的肺部疾病，由吸入 微生物抗原，在其诊断、发病机制、 和治疗。本研究的总体目标是识别和表征抗原 与 MWF 分枝杆菌 M.immunogenum 的 HP 诱导潜力相关 (MI) 和 M. chelonae (MC) 并评估它们在 HP 免疫诊断和 暴露评估。在之前的融资周期中，我们隔离了多种菌株 两个物种的（基因型）具有可变的抗原特征。我们将测试我们的 假设商业中普遍存在的 MWF 分枝杆菌菌株中的抗原多样性 MWF 负责差异性诱导 HP 症状和潜在免疫 反应，并且负责的特定抗原可以构成更多的基础 信息诊断以及个人和环境暴露评估。这 具体目标是： (1).根据 MI 和 MC 菌株的关键抗原来识别它们 在 HP 优化小鼠模型中与宿主免疫系统的相对相互作用； （2）。通过克隆和蛋白质重组生产已鉴定的关键抗原 特异性抗体的表达和产生； （3）。调查具体的潜力 用于早期个人暴露评估和有症状的免疫诊断的抗原 与无症状个体相比； （4）。评估特定抗原的潜力 MWF 分枝杆菌用于环境暴露评估（液体监测）。相对的 MI (6) 和 MC (4) 分离的不同基因型的免疫原性将是 基于 HP 诱导潜力和细胞介导的免疫反应进行比较 我们优化的小鼠模型和推定的蛋白质抗原将通过以下方式鉴定 差异免疫蛋白质组学分析。重组表达的抗原将是 使用小鼠模型和人类评估其免疫诊断潜力 受试者，特别是在区分无症状（暴露）与 有症状（HP 患者）和环境暴露评估。由此产生的 信息将通过提供一套分枝杆菌工具来帮助 NORA 实现目标 暴露评估和HP免疫诊断；这些成果将有利于未来 流行病学研究以及预防（疫苗接种）和干预措施的发展 小额信贷批发基金长期暴露策略。