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（由申请人提供）：机械工人的职业性过敏性肺炎（HP）与经常定植于现代水基金属加工液（MWF）的分枝杆菌有关。HP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表征与MWF分枝杆菌M种HP诱导潜力相关的抗原。immunogenum（MI）和M.并评估其用于HP免疫诊断和暴露评估的潜力。在之前的资助周期中，我们已经分离出两种具有可变抗原特征的物种的多个菌株（基因型）。我们将检验我们的假设，即商业MWF中普遍存在的MWF分枝杆菌菌株中的抗原多样性负责差异诱导HP症状和潜在的免疫应答，并且负责的特异性抗原可以形成更多信息诊断以及个人和环境暴露评估的基础。具体目标是：（1）。在优化的HP小鼠模型中，基于MI和MC株与宿主免疫系统的相对相互作用，鉴定MI和MC株中的关键抗原;（2）。通过克隆和蛋白表达重组生产鉴定的关键抗原并产生特异性抗体;（3）.探讨特异性抗原在有症状和无症状个体中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用于环境暴露评估（液体监测）的潜力。将使用我们优化的小鼠模型，基于HP诱导潜力和细胞介导的免疫反应来比较分离的不同基因型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来鉴定推定的蛋白质抗原。将使用小鼠模型和人类受试者评价重组表达的抗原用于免疫诊断的潜力，特别是在无症状（暴露）与有症状（HP患者）的区分以及环境暴露评估方面。由此产生的信息将有助于诺拉的目标，提供一套工具，分枝杆菌暴露评估和HP免疫诊断;这些结果将有助于未来的流行病学研究和发展的预防（疫苗接种）和干预战略的MWF暴露的长期。 公共卫生关系：现代金属加工液中的非结核分枝杆菌（NTM）与职业性呼吸道疾病有关。NIOSH和其他团体最近的研究将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。HP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，MWF分枝杆菌的特异性抗原的表征和HP免疫诊断和暴露评估的潜力进行评估，将有利于制定先发制人的措施和干预策略MWF相关的职业环境。