IMMUNE REGULATION IN TOXOPLASMOSIS AND OTHER OPPORTUNISTIC INFECTIONS

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The overall aim of this project is to analyze the immune response to Toxoplasma gondii and other opportunistic infections in order to define which cellular immune components and parasite target antigens are involved in the control of infection and its breakdown in immunocompromised hosts. Progress was made this year in the following areas: A. Demonstration of a superantigen activity in Toxoplasma gondii. Tachyzoites were shown to possess molecule(s) which stimulate proliferation of and IFN-gamma synthesis by splenocytes from uninfected animals. This activity, which fulfills all of the major criteria of a superantigen, may help explain both the early induction of cell-mediated immunity by T. gondii and the genetics of susceptibility to disease. B. Role of IL-12 in innate resistance. The induction of IL-12 was shown to be critical for the early IFN-gamma-dependent resistance of mice to acute infection but less important or non-essential for the prevention of disease reactivation. C. Studies on mechanisms of monokine induction by T. gondii. The triggering of the monokines TNF-alpha and IL-12 by T. gondii was shown to be independent of macrophage Lps receptors but to involve a similar signal transduction pathway. T. gondii was shown to be capable of stimulating HIV replication in virally infected human monocytes or macrophages from transgenic mice containing integrated provirus.