Improved Clearance of Mycobacterium avium Upon Disruption of the Inducible Nitric Oxide Synthase Gene

• Published in: The Journal of immunology (1950) Vol. 162; no. 11; pp. 6734 - 6739
• Main Authors: Gomes, M. Salome, Florido, Manuela, Pais, Teresa F, Appelberg, Rui
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.06.1999
• Subjects: Animals; Female; Interferon-gamma - biosynthesis; Interferon-gamma - physiology; Macrophages - enzymology; Macrophages - immunology; Macrophages - microbiology; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Knockout; Mycobacterium avium; Mycobacterium avium - growth & development; Mycobacterium avium - immunology; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase Type II; Species Specificity; Tuberculosis - enzymology; Tuberculosis - immunology; Tuberculosis - microbiology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.162.11.6734

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-gamma and TNF-alpha 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-gamma 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.