Novel Mycoplasma pneumoniae Toxin as Mediator of Airway Dysfunction in Mice

新型肺炎支原体毒素作为小鼠气道功能障碍的介质

• 批准号: 8126241
• 负责人: ROBERT DOUG HARDY
• 金额: $ 21.36万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8126241
• 关键词: Acute; Acute respiratory infection; Address; Adult; Affect; Animal Model; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Antibodies; Asthma; Bacteria; Bacterial Proteins; Biological Assay; Child; Chlamydophila pneumoniae; Chronic; Clinical Trials; Control Animal; Disease; Exhibits; Exposure to; Functional disorder; Gene Expression; Goals; Growth Factor; Histologic; Histopathology; Human; Immune; Immune response; Immunoglobulins; In Vitro; Inbred BALB C Mice; Infection; Inflammation; Investigation; Laboratories; Link; Literature; Long-Term Effects; Lung; Mediating; Mediator of activation protein; Methods; Microbiology; Modeling; Molecular; Mucous Membrane; Mus; Mycoplasma; Mycoplasma pneumoniae; Ovalbumin; Passive Immunization; Pathogenesis; Pathology; Phase; Physiological; Play; Pneumonia; Production; Protein Synthesis Inhibitors; Proteins; Recombinants; Research; Research Personnel; Respiratory Tract Infections; Role; Specimen; Therapeutic Intervention; Toxin; Work; airway hyperresponsiveness; airway inflammation; airway obstruction; chemokine; clinically relevant; cytokine; design; dosage; in vivo; inhibitor/antagonist; mouse model; mutant; novel; pulmonary function; respiratory; response

There is growing evidence linking M. pneumoniae respiratory infection and the inception, exacerbation, and chronicity of asthma in a subset of asthmatics. However, the pathogenic microbiologic mechanisms involved in this link have not been well characterized. Of great significance, Drs. Baseman and Kannan have now identified a novel M. pneumoniae toxin, CARDS TX. Our consortium of researchers (Drs. Baseman, Coalson, Dube, Kannan, Peters, and Hardy) has preliminary evidence of CARDS TX playing a pathogenic role in the airway inflammation, airway obstruction, airway hyperreactivity associated with respiratory M. pneumoniae infection. The hypothesis for the proposed research is that CARDS TX mediates the ability of M. pneumoniae to induce acute asthma exacerbations and is responsible for the deleterious long-term effects of mycoplasma respiratory tract infection. In addition, we hypothesize that therapeutic interventions directed against CARDS TX will ameliorate M. pnet/mon/ae-associated reactive airway disease and asthma. Briefly, the Specific aims are to 1) understand the specific contribution of active CARDS TX to the airway obstruction, hyperreactivity, and inflammation observed in M. pneumoniae respiratory infection, 2) determine if the host immune response to CARDS TX is protective against the respiratory manifestations of M. pneumoniae infection, and 3) determine the effect of bacterial protein synthesis inhibitor therapy on CARDS TX protein production in M. pneumoniae respiratory infection. The long-term goal of these investigations is to develop disease modifying strategies to treat children and adults with mycoplasma-associated reactive airway disease and asthma. This project focuses on investigating the novel M. pneumoniae toxin, CARDS TX, in our established acute and chronic murine model of M. pneumoniae respiratory infection in which airway inflammation, airway obstruction, and airway hyperreactivity have been previously characterized by our laboratory. BALB/c mice will be exposed to M. pneumoniae (wild-type and CARDS TX null mutant) or recombinant CARDS TX to determine the contribution of CARDS TX to the airway manifestations of M. pneumoniae infection. In addition, therapeutic interventions directed against CARDS TX will be assessed in our murine model with the goal of translational applicability to the treatment of reactive airway disease and asthma associated with M. pneumoniae in children and adults.

越来越多的证据表明M。肺炎呼吸道感染和发病，加重， 哮喘患者的慢性化。然而，致病微生物机制涉及 在这一联系中，还没有得到很好的描述。具有重要意义的是，贝斯曼博士和凯南博士 发现了一种新的M.肺炎毒素（Pneumoniae toxin，Pneumoniae TX）。我们的研究人员联盟（Baseman博士， Coalson、Dube、Kannan、Peters和哈代）有初步证据表明，BTX在致病性 作用于气道炎症、气道阻塞、气道高反应性与呼吸道M. 肺炎感染。这项研究的假设是，TXB 2介导了 M.肺炎引起急性哮喘恶化，并负责有害的长期 支原体对呼吸道感染的影响。此外，我们假设治疗干预 针对MITTX将改善M。PNET/MON/AE相关的反应性气道疾病和哮喘。 简而言之，具体目标是1）了解活性TXB 2对气道的具体贡献 在M.肺炎呼吸道感染，2）确定 如果宿主对MITTX的免疫应答对M. 肺炎感染，和3）确定细菌蛋白合成抑制剂治疗对肺炎的影响 在M.肺炎呼吸道感染。这些调查的长期目标是 制定疾病改善策略，治疗儿童和成人支原体相关反应性肺炎， 呼吸道疾病和哮喘。本课题主要研究小说M.肺炎毒素 TX，在我们建立的M.肺炎呼吸道感染， 气道炎症、气道阻塞和气道高反应性先前已被表征为 我们的实验室BALB/c小鼠将暴露于M.肺炎杆菌（野生型和HSTX无效突变体）或 重组MITTX以确定MITTX对M. 肺炎感染。此外，将在以下研究中评估针对BTX的治疗干预措施： 我们的鼠模型的目标是转化适用于治疗反应性气道疾病， 哮喘与M.肺炎在儿童和成人。