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Inducible Nitric Oxide Synthase Is Not Required for Long-Term Vaccine-Based Immunity Against Toxoplasma gondii¹

Departments of Medicine and Microbiology, Dartmouth Medical School, Lebanon, NH 03756

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

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