Tularemia: Pathogenesis and Host Response

兔热病：发病机制和宿主反应

• 批准号: 7092526
• 负责人: Karl E Klose
• 金额: $ 121.14万
• 依托单位: UNIVERSITY OF TEXAS SAN ANTONIO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-08 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7092526
• 关键词: Francisella tularensis; bioterrorism /chemical warfare; clinical research; host organism interaction; immune response

DESCRIPTION (provided by applicant): Francisella tularensis can cause serious illness and death in humans. F. tularensis is considered to be one of the most likely bioweapons due to ease of dissemination through aerosolization, and the high morbidity and mortality associated with inhalation tularemia. There is currently no tularemia vaccine licensed for general use, and thus human populations are at significant risk from the illicit use of F. tularensis. Very little is known about F. tularensis pathogenesis and host response, and thus fundamental research into F. tularensis biology is critical for the future development of therapeutics and vaccines against tularemia. We have assembled a group of integrated research projects focused on Francisella pathogenesis and immunity from researchers at the University of Texas San Antonio and the University of Texas Health Science Center in San Antonio. The individual projects are designed to be highly integrated with the other projects, and ultimately lead to a synergy that will propel our knowledge of this potential bioweapon such that new antimicrobial strategies can be developed. Virtually nothing is known about aerosol infections of F. tularensis subsp. tularensis (Type A), the most likely bioweapon form of tularemia, and thus this program project focuses almost exclusively on this form of tularemia. Our integrated bacteriological and immunological research approach involves four research projects and three support cores. These projects are designed to 1. identify essential and virulence factors of F. tularensis, 2. detail the immunology of inhalation tularemia in situ, 3. characterize the role of Toll-like receptors in host response, and 4. identify T cell epitopes and characterize T cell mediated responses to F. tularensis. These projects will be supported by an administrative core, a genomics core, and an immunomicroscopy core. The collaborative interactions of the investigators will ultimately lead to a dramatic increase in our understanding of pathogen-host interactions during F. tularensis subsp. tularensis aerosol infections, and facilitate the development of novel therapeutics and vaccines to combat weaponized tularemia.

描述（由申请人提供）：土拉菌可导致人类严重疾病和死亡。由于易于通过雾化传播，以及吸入性土拉菌病的高发病率和死亡率，土拉菌病被认为是最有可能的生物武器之一。目前还没有许可普遍使用的土拉菌病疫苗，因此，人群面临非法使用土拉菌病的重大风险。目前对土拉菌病的发病机制和宿主反应知之甚少，因此对土拉菌病生物学的基础研究对未来土拉菌病的治疗方法和疫苗的开发至关重要。我们汇集了一组来自德克萨斯大学圣安东尼奥分校和德克萨斯大学圣安东尼奥健康科学中心的研究人员对弗朗西斯菌发病机制和免疫的综合研究项目。单个项目被设计成与其他项目高度整合，并最终导致协同作用，这将推动我们对这种潜在生物武器的了解，从而可以开发新的抗菌策略。事实上，人们对土拉菌亚种的气溶胶感染一无所知。土拉菌病（A型），最可能是土拉菌病的生物武器形式，因此该项目几乎只关注这种形式的土拉菌病。我们的细菌学和免疫学综合研究方法涉及四个研究项目和三个支持核心。这些项目被设计成1。鉴定土拉菌的必要和毒力因子；2 .吸入性原位土菌病的免疫学研究；表征toll样受体在宿主反应中的作用；鉴定T细胞表位和表征T细胞介导的对土拉菌病的反应。这些项目将由一个行政核心、一个基因组核心和一个免疫显微镜核心提供支持。研究人员的合作互动将最终导致我们对土拉菌亚种期间病原体-宿主相互作用的理解急剧增加。土拉菌病气溶胶感染，并促进新疗法和疫苗的发展，以对抗武器化土拉菌病。