| Email: lukehart@u.washington.edu |
The Lukehart laboratory focuses on the pathogenesis of syphilis and the immune response to Treponema pallidum in humans and in animal models. The current major interest is the newly-identified polymorphic tpr gene family of T. pallidum, which comprises 2% of the T. pallidum genome and is hypothesized to encode surface-exposed antigens that are major targets of the protective immune response, may be involved in immune evasion, and are promising vaccine candidates. The possibility that these genes confer antigenic variation in T. pallidum, thus permitting persistence of the organism in immunocompetent hosts is being explored. Studies to date have indicated that the protective immune response to Treponema pallidum is mediated by Th1-type CD4+ lymphocytes and infiltrating macrophages. Ongoing projects in the laboratory include the cloning and characterization of major T cell antigens of T. pallidum and investigation of cytokine induction by these antigens.The laboratory is also working to identify the surface molecules that are targets of opsonization and to define the kinetics of and requirements for bactericidal activity by macrophages. Lastly, invasion of the central nervous system by T. pallidum occurs in the early weeks of infection. The laboratory is exploring the molecular basis for neuroinvasion, the immunologic response to T. pallidum within the CNS, and the efficacy of recommended therapy for CNS syphilis in immunocompetent and HIV-infected patients.