Immunopathogenesis of Coxiella pneumonia
Collaborating Institution: Montana State University (MSU), Bozeman, MT
Principal Investigator: Allen Harmsen, Ph.D.
Collaborators and Core Labs:
a) Coxiella Cultivation Core – University of Montana (UM), Missoula, MT
b) David Pascual, Ph.D. – MSU
c) Mark Jutila, Ph.D. – MSU
d) Mike Minnick, Ph.D.– UM
e) James Samuel, Ph.D. – Texas A&M University, College Station, TXExpected Product: Novel immunotherapies and therapeutic approaches against Coxiella burnetii.
Introduction:
Because Coxiella burnetii is such a difficult organism to work with, there is little known about the immunopathogenesis of Q fever pneumonia. 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-γ, 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:
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.