Toxoplasma gondii is an important parasitic infection causing much morbidity and mortality in patients with primary or acquired immunodeficiencies. Because production of IFNg is crucial in both innate and adaptive immunity to toxoplasmosis, understanding the molecular mechanisms involved in the induction of this cytokine will be paramount to developing novel treatment strategies. The transcription factor NF-kB has been implicated in the production of IFNg by both NK and T cells; principal mediators of innate and adaptive immunity to toxoplasmosis respectively. Using retroviral gene transfection to selectively inhibit NF-kB signaling, it will be possible to assess the role of this transcription factor in the production of IFNg by NK cells in vitro. In addition, by reconstituting sublethally irradiated RAG -/- mice with these virally transfected cells, the importance of NF-kB signaling in innate immunity to toxoplasmosis can be determined in vivo. Furthermore, by employing a transgenic mouse model in which NF-kB signaling is inhibited in T cells, the role of NF-kB activation in T cell mediated resistance to T. gondii infection can be determined.
