INDUCIBLE NITRIC-OXIDE SYNTHASE IS NOT REQUIRED FOR LONG-TERM VACCINE-BASED IMMUNITY AGAINST TOXOPLASMA-GONDII

Induction of reactive nitrogen intermediates by IFN-gamma is presumed an important mechanism of host resistance against acute and chronic in fection with Toxoplasma gondii, Although nitric oxide (NO) has been sh own to be important in the control of parasite replication in vivo, th e role of this molecule in vaccine-based immunity against T, gondii is unknown. Mice with a targeted disruption of inducible NO synthase (iN OS) were immunized with an avirulent temperature-sensitive strain of t his parasite (ts-4). Both the parental C57BL/6 and the iNOS(-/-) mice survived infection with the ts-4 mutant. Oral challenge of the vaccina ted mice with a lethal dose of cysts containing bradyzoites resulted i n reduced parasite burden and increased survival compared with nonvacc inated control mice, Host immunity in the iNOS(-/-) mice, similar to t hat observed in the parental strain, appears dependent upon both IFN-g amma and CD8(+) T cells. These findings suggest that although vaccine- based long-term immunity against T. gondii is dependent upon the induc tion of IFN-gamma, it does not rely upon the anti-microbial effect of NO.