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. ? ?
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