Tularemia: Pathogenesis and Host Response

兔热病：发病机制和宿主反应

• 批准号: 7255387
• 负责人: Karl E Klose
• 金额: $ 118.16万
• 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/7255387
• 关键词: Tularemia; Pathogenesis; Host; 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）：土拉弗朗西斯菌可导致人类严重疾病和死亡。由于土拉菌易于通过雾化传播，并且吸入性兔热病具有较高的发病率和死亡率，因此土拉菌被认为是最有可能的生物武器之一。目前还没有获准普遍使用的兔热病疫苗，因此人类面临着非法使用兔拉热病疫苗的巨大风险。人们对土拉菌的发病机制和宿主反应知之甚少，因此对土拉菌生物学的基础研究对于未来针对土拉菌病的治疗和疫苗的开发至关重要。我们从德克萨斯大学圣安东尼奥分校和圣安东尼奥德克萨斯大学健康科学中心的研究人员那里组建了一组专注于弗朗西斯菌发病机制和免疫的综合研究项目。各个项目的设计目的是与其他项目高度整合，并最终产生协同作用，从而推动我们对这种潜在生物武器的了解，从而开发新的抗菌策略。事实上，对于土拉弗拉菌亚种的气溶胶感染一无所知。土拉热病（A 型）是最有可能的生物武器形式的土拉热病，因此该计划项目几乎完全专注于这种形式的土拉热病。我们的综合细菌学和免疫学研究方法涉及四个研究项目和三个支持核心。这些项目旨在 1. 鉴定土拉菌的必需因子和毒力因子，2. 详细介绍吸入性土拉菌原位免疫学，3. 表征 Toll 样受体在宿主反应中的作用，以及 4. 鉴定 T 细胞表位和表征 T 细胞介导的对 F. tularensis 的反应。这些项目将得到管理核心、基因组学核心和免疫显微镜核心的支持。研究人员的协作互动最终将导致我们对土拉弗拉菌亚种期间病原体与宿主相互作用的理解急剧增加。土拉热病气溶胶感染，并促进开发新疗法和疫苗来对抗武器化土拉热病。