Role of unique ADP-ribosylating vacuolating Mycoplasma pneumoniae toxin in asthma

圣安东尼奥/达拉斯哮喘和过敏性疾病合作研究中心代表了一个综合， 合作和创新的多学科努力，以调查独特的肺炎支原体的作用， 哮喘和相关气道疾病中的毒素。这种毒素被命名为社区获得性呼吸窘迫 综合征毒素（Syndrome Toxin，简称CTTX）显著复制促炎细胞因子/趋化因子谱， 组织病理学检查见M.肺炎感染。德克萨斯大学和 位于圣安东尼奥的健康科学中心和位于达拉斯的德克萨斯大学西南医学院 结合了4个项目，重点是基础，临床和动物建模策略，有2个支持核心 （行政和病理），提出了一个全新的方法来界定之间的关系M。 肺炎和哮喘的发病机制。大量的文献，积累了超过35 年，连接M。肺炎支原体与哮喘发作、加重和慢性化之间的关系，但没有单一的支原体 毒力决定子或支原体分子已被证明是症状的媒介 和相关的病理学。缺乏可定义的M。肺炎致病因素大大阻碍了 了解M。肺炎影响气道疾病的发生和发展。这是 特别是在复杂的疾病，如哮喘，其中遗传，免疫，传染性和 环境变量似乎影响疾病的发展和进展。AADCRC的一个主要重点是 将ADP-核糖基化、空泡化M. pneumoniae pneumon通过这样 通过这样做，我们希望证明，在人类哮喘相关的病理生物学中， （项目3）和实验感染或中毒小鼠（项目1和2）。因此，我们打算（a） 通过新的有效的靶向哮喘诊断方法， 使用患者的鼻粘膜进行评估（ELISA、免疫组织化学、抗原捕获和PCR方法） 灌洗液、痰和血清样品;（B）使用M.肺炎感染和肺炎支原体感染 中毒检查哮喘的急性和慢性阶段和治疗干预以及 BTX对气道高反应性影响;和（c）进一步表征 开发有效和快速的诊断方法，以帮助治疗和控制哮喘， 相关的病理。每个项目和核心的主要研究人员都有良好的跟踪记录和专业知识， 哮喘、气道相关病理、免疫发病机制和M.肺炎生物学和毒力以及 合作和共同出版的历史。

The San Antonio/Dallas Asthma and Allergic Diseases Cooperative Research Center represents an integrative, collaborative and innovative multidisciplinary effort to investigate the role of a unique Mycoplasma pneumonias toxin in asthma and related airway diseases. This toxin, designated Community Acquired Respiratory Distress Syndrome Toxin (CARDS TX) remarkably replicates the proinflammatory cytokine/chemokine profiles and histopathology that accompany M. pneumoniae infection. This consortium between The University of Texas Health Science Center at San Antonio and The University of Texas Southwestern Medical School in Dallas combines 4 projects, which focus on basic, clinical and animal modeling strategies, with 2 support cores (administrative and pathology) to bring a totally new approach to defining the relationship between M. pneumoniae and the pathogenesis of asthma. A substantial literature, which has accumulated over thirty-five years, connects M. pneumoniae to onset, exacerbation, and chronicity of asthma, yet no single mycoplasma virulence determinant, or mycoplasma molecule for that matter, has been shown to be a mediator of symptoms and associated pathologies. This lack of definable M. pneumoniae pathogenic factors has greatly hampered an understanding of how M. pneumoniae influences the development and progression of airway diseases. This is especially challenging in complex diseases like asthma, where genetic, immunologic, infectious and environmental variables appear to affect disease development and progression. A major focus of the AADCRC is to directly link the biochemical, molecular and immunological properties of the ADP-ribosylating, vacuolating M. pneumoniae CARDS TX (Project 4), to diagnosis and treatment of asthmatic patients (Projects 3 and 4). By so doing, we hope to demonstrate that CARDS TX is a key mediator of asthma-associated pathobiology in humans (Project 3) and in experimentally infected or intoxicated mice (Projects 1 and 2). Therefore, we intend to (a) directly connect CARDS TX to asthma pathogenesis through novel and effective CARDS TX-targeted diagnostic assessments (ELISA, immunohistochemistry, antigen capture and PCR methodologies) using patient's nasal lavage, sputum and serum samples; (b) use mouse models of M. pneumoniae infection and CARDS TX intoxication to examine both acute and chronic stages of asthma and therapeutic interventions as well as the impact of CARDS TX on airway hyper-reactivity; and (c) further characterize ADP-ribosylating activities of CARDS TX and develop effective and rapid diagnostics to assist in the treatment and control of asthma and related pathologies. The key investigators of each project and core have strong track records and expertise in asthma, airway-related pathologies, immunopathogenesis and M. pneumoniae biology and virulence as well as a history of collaboration and co-publication.