ENCEPHALITOZOAN CUNICULI--HOST IMMUNITY AND PATHOGENESIS

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Microsporidia are obligate intracellular protozoan parasites which cause wide variety of opportunistic infections in AIDS patients. The most common microsporidium associated with AIDS, Enterocytozoon beneusi, causes chronic diarrhea in the HIV-infected individuals. However, an animal model for E. beneusi is not available at present. Most of the experimental studies on microsporidia have been carried out on with Encephalitozoon cuniculi. This microsporidium, which commonly infects rodents, has been reported in humans as well. Several reports of disseminated E. cuniculi infection in HIV-infected patients have appeared recently. E. cuniculi is also very closely related to other microsporidia like Encephalitozoon hellum and Encephalitozoon intestinalis, which are also known to cause complications in AIDS individuals. Very little is known about the immune mechanisms against microsporidial infection in the normal host. The cellular immunity appears to be important for protection against an E. cuniculi challenge. Preliminary studies suggest that CD8+ T cells are an essential component of the immune response. Therefore, the detailed analysis of CD8+ T cell immunity is essential for understanding the immunoprotective mechanism against E. cuniculi infection. The first specific aim in this project will be to evaluate the kinetics of CD8+ T cell response during the course of E. cuniculi infection. The difference in this response between the resistant and susceptible species of mice will be determined and compared; the cytotoxic activity of the CD8+ T cells from the infected normal and immunocompromised animals will be assayed. The second specific aim is to determine the efficacy of the adoptive transfer of immune CD8+ T cells into infected immunocompromise host. Next, the length of time for which the immune CD8+ T cells can retain their activated/memory state in the naive immunocompromised host will be determined. In the third specific aim the role of gamma/delta T cells and the CD4+ T cells in the induction and maintenance of CD8+ T cell immunity will be evaluated. These studies will enable extrapolation to the immune mechanisms against other microsporidia, like E. beneusi, which is more frequently encountered by AIDS patients.