Improved Clearance of <i>Mycobacterium avium</i> Upon Disruption of the Inducible Nitric Oxide Synthase Gene

Abstract

Abstract Mice genetically deficient in the inducible NO synthase gene (iNOS−/−) were used to study the role played by NO during infection by Mycobacterium avium. iNOS−/− macrophages were equally able to restrict M. avium growth in vitro following stimulation by IFN-γ and TNF-α as macrophages from wild-type mice. In vivo, the infection progressed at similar rates in wild-type and NO-deficient mice during the first 2 mo of infection, but the latter mice were subsequently more efficient in clearing the mycobacteria than the former. The increased resistance of iNOS−/− mice was associated with higher IFN-γ levels in the serum and following in vitro restimulation of spleen cells with specific Ag, increased formation of granulomas and increased survival of CD4+ T cells. We show that NO is not involved in the antimycobacterial mechanisms of M. avium-infected macrophages and, furthermore, that it exacerbates the infection by causing the suppression of the immune response to the pathogen.