Growth-inhibitory effects of interferon-gamma on Neospora caninum in murine macrophages by a nitric oxide mechanism.

To clarify the effector pathway of Neospora caninum growth-inhibitory activity induced by interferon-gamma (IFN-gamma) in murine macrophages we examined the relationship between IFN-gamma and nitric oxide (NO). Production of NO was enhanced in cultures of macrophages supplemented with IFN-gamma, and dose-dependent growth inhibition was observed. These findings suggest that the inhibitory activity induced in macrophages by IFN-gamma is mediated NO molecules. A competitive inhibitor of the L-arginine-dependent effector pathway, NG-monomethyl-L-arginine, virtually abolished the inhibitory effects induced by IFN-gamma. From this finding it appears that the inhibitory effects induced by IFN-gamma in macrophages may be mediated by an L-arginine-dependent effector pathway that involves NO production. In vivo, mice with a targeted disruption of the inducible NO synthase gene (iNOS-/-) were more susceptible than wild-type mice to N. caninum. Therefore, the production of NO in macrophages induced by IFN-gamma is an important mechanism for the killing of intracellular N. caninum.