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: 7886344
• 负责人: Jagjit S Yadav
• 金额: $ 39.99万
• 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/7886344
• 关键词: MWF; Mycobacteria; antigens; occupational; hypersensitivity

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Non-tuberculous mycobacteria (NTM) colonizing modern metalworking fluids (MWFs) have been associated with occupational respiratory illnesses. Recent studies by NIOSH and other groups have linked MWF mycobacteria with occupational hypersensitivity pneumonitis (HP) in exposed machine workers. HP is an immune-mediated lung disease caused by inhalation of microbial antigens. Hence, characterization of specific antigens in MWF mycobacteria and evaluation of their potential for HP immunodiagnosis and exposure assessment will facilitate development of pre-emptive measures and intervention strategies in MWF-associated occupational environments.

描述(申请人提供)：机械工人中的职业过敏性肺炎(HP)与分枝杆菌有关，这种分枝杆菌经常在现代水基金属加工液(MWF)中定植。幽门螺杆菌是一种由吸入微生物抗原引起的免疫介导的肺部疾病，在其诊断、发病机制和治疗方面的研究相对较少。本研究的总体目标是鉴定和鉴定MWF分枝杆菌种免疫分枝杆菌(MI)和龟分枝杆菌(MC)诱导幽门螺杆菌的相关抗原，并评价其在幽门螺杆菌免疫诊断和暴露评估中的潜力。在之前的资助周期中，我们已经分离出这两个物种具有不同抗原性的多个菌株(基因类型)。我们将检验我们的假设，即商业MWF中流行的MWF分枝杆菌菌株的抗原多样性负责不同地诱导HP症状和潜在的免疫反应，并且负责的特定抗原可能形成更多信息的诊断和个人和环境暴露评估的基础。具体目标是：(1)。在优化的幽门螺杆菌小鼠模型中，根据MI和MC菌株与宿主免疫系统的相对相互作用，确定它们的关键抗原；(2)通过克隆、蛋白表达和产生特异性抗体，重组生产已鉴定的关键抗原；研究特定抗原对有症状和无症状个体的早期个人暴露评估和免疫诊断的潜力；(4)评价MWF分枝杆菌特异性抗原(S)在环境暴露评估(流体监测)中的潜力。利用我们优化的小鼠模型，基于幽门螺杆菌诱导能力和细胞免疫应答，比较不同基因型MI(6)和MC(4)的相对免疫原性，并通过差异免疫蛋白质组学分析鉴定可能的蛋白质抗原。将利用小鼠模型和人类受试者评估重组表达的抗原用于免疫诊断的可能性，特别是在区分无症状(暴露)和有症状(HP患者)以及环境暴露评估方面。由此产生的信息将通过提供一套分枝杆菌暴露评估和HP免疫诊断工具来帮助Nora实现目标；这些结果将促进未来的流行病学研究和长期MWF暴露的预防(疫苗接种)和干预策略的发展。 公共卫生相关性：现代金属加工液(MWF)中的非结核分枝杆菌(NTM)与职业性呼吸道疾病有关。NIOSH和其他研究小组最近的研究将MWF分枝杆菌与接触机器工人的职业性过敏性肺炎(HP)联系起来。幽门螺杆菌是一种由吸入微生物抗原引起的免疫介导的肺部疾病。因此，鉴定MWF分枝杆菌的特异性抗原并评估其在Hp免疫诊断和暴露评估中的潜力，将有助于在MWF相关职业环境中制定预防措施和干预策略。