Immunopathogenesis of Coxiella pneumonia

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Because Coxiella burnetii is such a difficult organism to work with, there is little known about the immunopathogenesis of Q fever pneumonia. Howeveer, from the little work that has been done in this area and from what is known about immune responses to other intracellular bacteria, we hypothesize that a T1- like T cell response, with the production of IFN-y, clears established Coxiella infection from the lung and, in addition, that a local immunoglobulin response in the lung can help the host to resist the initiation of infection after aerosol exposure to the pathogen. To address this hypothesis we propose to: 1. to define the cellular and humoral host immune responses to both primary and secondary Coxiella infection and to correlate the host response with the kinetics of Coxiella growth and clearance; 2. to determine the cellular and humoral mechanisms responsible for primary and secondary (memory) resistance to Coxiella', 3. to determine whether mucosal immunization is more effective than systemic immunization in generating long term effective immunity to Coxiella. Results from the studies proposed here will lead to a better understanding of the immunopathogenesis of Coxiella pneumonia. Such knowledge is crucial to the rational design of immunotherapies against this infection. Project Interactions: This project (Project 3) will supply phase 1 Coxiella isolated from infected mice to Project 1 for the analysis of gene expression. The results of this project will be shared with Projects 2 and 4 who will consider them in the formulation of their vaccines. Project 3 will also work closely with Project 2 in the performance of the in vivo testing of the efficacy of candidate adjuvants. Similarly, Project 3 will work closely with Project 4 in determining efficacy of candidate vaccine constructs and delivery systems. Lastly, results from Project 1 on how Coxiella responds to the host will be important in understanding how the host responds to Coxiella (Project 1).