MWF Mycobacteria Antigens in Occupational Hypersensitivity Pneumonitis

项目摘要 机械工人的职业性过敏性肺炎（HP）已被 与经常在现代水基金属加工中定植的分枝杆菌有关 流体（MWF）。HP是一种免疫介导的肺病， 微生物抗原，并且在其诊断，发病机理， 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.免疫原 (MI)和M.并评估其用于HP免疫诊断的潜力， 暴露评估。在之前的融资周期中，我们已经分离出多种菌株， （基因型）具有可变抗原特征的两个物种。我们将测试我们的 商业上流行MWF分枝杆菌菌株中的抗原多样性 MWF负责差异诱导HP症状和潜在的免疫反应。 反应，而负责的特异性抗原可以形成更多的基础， 信息诊断以及个人和环境暴露评估。的 具体目标是：（1）。根据MI和MC菌株的特征， 在优化的HP小鼠模型中与宿主免疫系统的相对相互作用; （二）、通过克隆和蛋白质重组生产鉴定的关键抗原 表达和产生特异性抗体;（3）.调查特定的潜力 用于早期个人暴露评估和有症状的免疫诊断的抗原 与无症状个体比较;（4）.评价特异性抗原的潜力 用于环境暴露评估的MWF分枝杆菌（液体监测）。相对 分离的MI（6）和MC（4）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应答进行比较， 我们优化的小鼠模型和推定的蛋白质抗原将通过 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模型评估其免疫诊断潜力。 受试者，特别是在无症状（暴露）与 症状（HP患者）和环境暴露评估。所得 这些信息将有助于诺拉的目标， 暴露评估和HP免疫诊断;这些结果将有助于未来 流行病学研究和预防（疫苗接种）和干预措施的发展 MWF长期暴露的策略。

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.