Sheila A. Lukehart, PhD
Professor of Medicine and Global Health, Adjunct Professor of Microbiology
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Syphilis is a global health problem, with a significant impact on infants and children due to congenital infection. This laboratory focuses on several aspects of the pathogenesis and immune response to syphilis and other treponemal infections in humans and in animal models. (1) 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. (2) Bacterial clearance in vivo results from ingestion and killing of opsonized treponemes by macrophages. The laboratory is currently working to identify the surface molecules that are targets of opsonization and to define the kinetics of and requirements for bactericidal activity by macrophages. (3) In collaboration with Drs. Arturo Centurion and Lorenzo Giacani, the lab has identified phase variation and antigenic variation of important surface molecules (e.g., opsonic targets) that permit immune evasion leading to chronic infection. Studies of the role of antigenic variation in syphilis reinfection are ongoing. (4) Comparative genetic and antigenic studies are being conducted on the various pathogenic treponemes, with the goal of identifying protective antigens and important virulence factors. (5) Development of a vaccine for syphilis is underway, with comparison of antigen cocktails and 3 test adjuvants in the rabbit model. (6) Invasion of the central nervous system by T. pallidum occurs in the early weeks of infection. With Dr. Christina Marra, the laboratory is exploring the immunologic response to T. pallidum within the CNS, and the efficacy of recommended therapy for CNS syphilis in immunocompetent and HIV-infected patients. In addition, mechanisms of neuroinvasion by T. pallidum are being investigated in the rabbit model.