Effect of Aging on Immunity to Tularemia

衰老对兔热病免疫的影响

• 批准号: 6874503
• 负责人: JUDY M TEALE
• 金额: $ 25.98万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2005-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6874503
• 关键词: Francisella tularensis; age difference; aging; antibiotics; attenuated microorganism; bacteria infection mechanism; bacterial cytopathogenic effect; bioterrorism /chemical warfare; confocal scanning microscopy; cytokine; fluorescence microscopy; green fluorescent proteins; histopathology; immune response; immunization; immunomodulators; immunosenescence; interleukin 12; laboratory mouse; macrophage; microarray technology; microorganism immunology; mutant; respiratory infections; tularemia

DESCRIPTION (provided by applicant): Many infectious diseases, especially respiratory diseases, are more frequent and severe among the elderly compared with the younger population. The long-term objective of this project is to compare infection and immunity in young and aged individuals using a mouse model of pulmonary tularemia. The causative agent of tularemia is Francisella tularensis. The biotype A strain of Francisella (Schu4) has been classified as a Category A bioterrorism agent because of its ease of transmission and high mortality rate when inhaled. As such, this project is significant for the areas of both aging and bioweapons. Infection by F.t. novicia and F.t. tularensis (Schu4) will be compared in young adult and aged mice using primarily targeted macroarrays followed by in situ methodologies involving 3 and 4 color fluorescence microscopy and confocal microscopy. The aims are to perform a kinetic analysis of the infectious disease process in young and aged mice. This will allow a systematic and simultaneous analysis of the immune cells, cytokines, location of the bacteria as it disseminates, and the resulting histopathology. In addition, the protective efficacy of two protective strategies as a result of aging will be tested including the use of attenuated mutants and the use of lL-12 as an adjuvant. The underlying hypothesis is that aged animals will exhibit a delayed innate/adaptive immune response and less protection from therapeutic strategies. The proposed experiments will provide important new insights into immunosenescence, immunity to intracellular respiratory bacteria, and potential strategies should Francisella be used as a bioweapon.

描述（由申请人提供）：与年轻人相比，许多传染病，尤其是呼吸道疾病，在老年人中更加频繁和严重。该项目的长期目的是使用肺部小鼠小鼠模型比较年轻和老年人的感染和免疫力。 Tularemia的病因是Francisella tularensis。 Francisella（Schu4）的生物型A菌株已被归类为一种生物恐怖剂，因为吸入时易于传播和高死亡率。因此，该项目对于衰老和生物武器的领域都很重要。 F.T.感染Novicia和F.T.将使用主要靶向宏观阵列的年轻小鼠和老年小鼠的年轻小鼠比较tularensis（Schu4），然后将涉及3和4彩色荧光显微镜和共聚焦显微镜的原位方法进行比较。目的是对年轻小鼠和老年小鼠的传染病过程进行动力学分析。这将允许对免疫细胞，细胞因子，细菌分散时的位置以及所得的组织病理学进行系统和同时分析。此外，将测试两种保护性策略的保护效果，包括使用衰减突变体和使用LL-12作为辅助物。基本的假设是，老年动物将表现出延迟的先天/适应性免疫反应，并更少保护治疗策略。提出的实验将为免疫衰老，对细胞内呼吸细菌的免疫提供重要的新见解，如果将方济各菌作为生物武器，则可能会提供潜在的策略。