Candidate human vaccines against Coxiella burnetii, the etiologic agent of Q fever, have been studied in animals and in man in order to evaluate the humoral and cellular mechanisms of pathogenesis. A. mice. Fractions of phase I C. burnetii which induce mitogenic hyporesponsiveness and negative modulation of C57BL/10 ScN lymphocytes have been identified and partially purified. An infection model using C57BL/6J (resistant) and A/J (sensitive) mice was successful in demonstrating a 1,000-fold difference in the lethal dose 50 and a 7,000-fold greater sensitivity of the A/J mouse to the effects of immunosuppression. The concurrence of pathogenic and immunosuppressive events with infection or vaccination suggested that these responses were linked. However, studies with the immunological status of BALB/c sublines and congenic strains after either infection or vaccination have shown that gross pathologic responses can be genetically unlinked from the immunological unresponsiveness. Splenic lymphocytes of BALB/c mice were suppressed after infection or vaccination, but only infection induced hepato-splenomegaly. The splenic lymphocytes produce soluble lymphokines and suppressors during a 48-hour in vitro incubation with c. burnetii antigens. The cell types involved in the immunomodulation bind C. burnetii antigen, adhere to nylon wool, and are not completely inactivated by anti-theta and complement. B. Humans. Specific T-cell unresponsiveness is an important factor in persistent Q fever. Lymphocyte unresponsiveness to Coxiella antigen in patients with Q fever endocarditis was antigen-specific and was mediated, in part, by glass adherent suppressor cells. Prevention of protaglandin E2 (PGE2) by indomethacin completely reversed the Coxiella-induced suppression. Thus, elicitation of suppressors was antigen-specific and involved a T-cell monocyte suppressor circuit. Significance. The objectives of this project are to define the genetic factors involved in susceptibility to infection and phase I vaccine in the mouse model and to characterize the virulence factors of Coxiella which induce pathological reactions in humans.
| Eells, Samantha J; Bharadwa, Kiran; McKinnell, James A et al. (2014) Recurrent urinary tract infections among women: comparative effectiveness of 5 prevention and management strategies using a Markov chain Monte Carlo model. Clin Infect Dis 58:147-60 |
