Improved clearance of Mycobacterium avium upon disruption of the inducible nitric oxide synthase gene

MS Gomes, M Flórido, TF Pais… - The Journal of …, 1999 - journals.aai.org
MS Gomes, M Flórido, TF Pais, R Appelberg
The Journal of Immunology, 1999journals.aai.org
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 …
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.
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