MWF Mycobacteria antigens in occupational hypersensitivity pneumonitis

项目总结 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居的分枝杆菌有关 流体(MWFS)。幽门螺杆菌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。这项研究的总体目标是鉴定和表征抗原 MWF分枝杆菌免疫原菌诱导幽门螺杆菌能力的研究 (MI)和龟分枝杆菌(MC)，并评价其在幽门螺杆菌免疫诊断和 暴露评估。在之前的资助周期中，我们分离出了多种菌株 (基因类型)具有不同抗原性的两个物种。我们将测试我们的 商业流行的MWF分枝杆菌菌株的抗原多样性假说 MWF负责不同程度地诱导Hp症状和潜在免疫 反应，负责的特定抗原可以形成更多的基础 信息性诊断以及个人和环境暴露评估。这个 具体目标是：(1)。根据心肌炎和甲型脑炎病毒株的关键抗原 幽门螺杆菌优化小鼠模型中与宿主免疫系统的相对相互作用； (2)。克隆和蛋白重组生产已鉴定的关键抗原 (3)特异性抗体的表达和产生；调查特定项目的潜力 用于早期个人暴露评估和症状免疫诊断的抗原 与无症状个体比较；猪传染性支气管炎特异性抗原(S)的潜力评价 用于环境暴露评估(流体监测)的MWF分枝杆菌。相对的 分离的不同基因型MI(6)和MC(4)的免疫原性将 基于幽门螺杆菌诱导潜能和细胞免疫应答的比较 我们优化的小鼠模型和可能的蛋白质抗原将通过 差异免疫蛋白质组学研究。重组表达的抗原将是 用小鼠模型和人类模型评估它们在免疫诊断中的潜力 受试者，特别是在区分无症状(暴露)和 症状(幽门螺杆菌患者)和环境暴露评估。由此产生的 信息将通过为分枝杆菌提供一套工具来帮助Nora实现目标 暴露评估和幽门螺杆菌免疫诊断；这些结果将促进未来 预防(接种)和干预的流行病学研究和发展 长期接触MWF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.