Tularemia: Pathogenesis and Host Response

描述（由申请人提供）：土拉热弗朗西斯菌可导致人类严重疾病和死亡。F.土拉菌病被认为是最有可能的生物武器之一，因为它易于通过雾化传播，而且与吸入性土拉菌病相关的发病率和死亡率很高。目前还没有许可用于一般用途的兔热病疫苗，因此人类群体面临着非法使用F.土拉热。关于F的知之甚少。土拉热菌的致病机理和宿主反应，从而为土拉热菌的基础研究奠定了基础。土拉菌生物学对于未来开发抗土拉菌病的治疗剂和疫苗至关重要。我们已经从德克萨斯大学圣安东尼奥和德克萨斯大学圣安东尼奥健康科学中心的研究人员那里收集了一组集中于弗朗西斯菌发病机制和免疫的综合研究项目。各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，对F.土拉热亚种土拉热病（A型），最有可能的生物武器形式的土拉热病，因此，本方案项目几乎完全侧重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F. tularensis，2.详细介绍了吸入性兔热病的免疫学特点，3.表征Toll样受体在宿主应答中的作用，和4.鉴定T细胞表位和表征T细胞介导的对F.土拉热。这些项目将得到一个行政核心、一个基因组学核心和一个免疫显微镜核心的支持。研究人员的合作互动将最终导致我们对F.土拉热亚种土拉菌气溶胶感染，并促进新的治疗和疫苗的开发，以打击武器化的土拉菌。

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.