Effect of Aging on Immunity to Tularemia

衰老对兔热病免疫的影响

• 批准号: 7033908
• 负责人: JUDY M TEALE
• 金额: $ 34.54万
• 依托单位: UNIVERSITY OF TEXAS SAN ANTONIO
• 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 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7033908
• 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（申请人提供）：与年轻人相比，许多传染病，特别是呼吸道疾病，在老年人中更常见、更严重。该项目的长期目标是使用肺兔热病小鼠模型来比较年轻人和老年人的感染和免疫力。土拉热病的病原体是土拉弗朗西斯菌。弗朗西斯菌 (Schu4) 生物型 A 菌株因其易于传播且吸入后死亡率高而被列为 A 类生物恐怖主义制剂。因此，该项目对于老龄化和生物武器领域都具有重要意义。 F.t. 感染诺维西亚和 F.t.将使用主要靶向的宏阵列，然后使用涉及 3 色和 4 色荧光显微镜和共聚焦显微镜的原位方法，在年轻成年和老年小鼠中比较 tularensis (Schu4)。目的是对年轻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、细菌传播时的位置以及由此产生的组织病理学进行系统且同步的分析。此外，还将测试两种保护策略对衰老的保护功效，包括使用减毒突变体和使用IL-12作为佐剂。基本假设是，老年动物会表现出延迟的先天/适应性免疫反应，并且对治疗策略的保护较少。拟议的实验将为免疫衰老、细胞内呼吸道细菌免疫以及弗朗西斯菌用作生物武器的潜在策略提供重要的新见解。