The proposed research will analyze the role of B cells and their products in resistance to Toxoplasma gondii infection in mice. Toxoplasmosis is a significant cause of morbidity/mortality in AIDS patients and congenitally infected individuals, and is also an important reasearch tool with which to analyze innate and acquired immunological mechanisms of host resistance to pathogenic microbes. Infection of B cell-deficient muMT mice has revealed that B cells are needed in order for mice to resist chronic primary T. gondii infection and to survive challenge with highly virulent parasites if previously vaccinated. Two hypotheses are proposed to explain the role of B cells in resistance to T. gondii. The proposed experiments will examine whether B cells are needed for the production of protective antibodies or for the regulation of T. gondii-induced T cells and cytokines having the potential to cause immunopathology. Experimental goals will be addressed by analysis of host cell and cytokine responses and histopathology in infected muMT and control B cell-sufficient mice. The ability of immune serum, together with immune T cells, to confer protection against a challenge infection with virulent tachyzoites will be addressed in adoptive immunization experiments. The resistance of vaccinated mice with mutated Fc receptor genes or C3, C4, or C5 complement genes will be examined in relation to the hypothesis that antibodies are essential to protection in this model. The potential for B cells to regulate cytokine production and the generation of T. gondii-specific T cells will be studied. Also, the role of B cells in protection against congenital T. gondii infection and the influence of Toxoplasma-specific antibodies on the resistance of mice infected as neonates will be analyzed.
