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

M. Salomé Gomes, Manuela Flórido, Teresa F. Pais, Rui Appelberg

Research output: Contribution to journalArticlepeer-review

119 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)6734-6739
Number of pages6
JournalJournal of Immunology
Volume162
Issue number11
Publication statusPublished - 1 Jun 1999
Externally publishedYes

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