Gene targeting demonstrates that inducible nitric oxide synthase is not essential for resistance to oral candidiasis in mice, or for killing of Candida albicans by macrophages in vitro.
BACKGROUND
Oral candidiasis is caused by opportunistic infections with the yeast Candida albicans. Previous studies have demonstrated important roles for innate immunity and T helper type 1-mediated inflammatory reactions in recovery from infection, with macrophages and neutrophils as key effector cells. Both effector cell types use the inducible isoform of nitric oxide synthase (iNOS) to generate candidacidal molecules, but it is not clear whether nitric oxide (NO) is an absolute requirement for candidacidal effector activity.


METHODS
In this study we directly investigated the role of iNOS-derived NO in resistance to murine experimental oral candidiasis, using iNOS knockout mice.


RESULTS
Knockout mice were no more susceptible to oral candidiasis than wild-type controls. Bone marrow-derived macrophages from the knockout mice killed C. albicans yeasts efficiently in vitro, and were still able to produce nitrites in an iNOS-independent manner, albeit less efficiently than wild-type controls. There were no significant differences in local mucosal production of interleukins 6, 12, 17A, or 23, interferon-gamma, or transforming growth factor-beta 24 h after oral challenge with C. albicans.


CONCLUSIONS
These data suggest that iNOS-derived NO is not required for resistance to oral candidiasis in vivo, and that bone marrow-derived macrophages may have iNOS-independent means of generating reactive nitrogen species.
Farah
C S
CS
Oral Biology and Pathology, School of Dentistry, The University of Queensland, St Lucia, Queensland, Australia. c.farah@uq.edu.au
Saunus
J M
JM
Hu
Y
Y
Kazoullis
A
A
Ashman
R B
RB
D000818:Animals; D002176:Candida albicans / Q000276:immunology; D002180:Candidiasis, Oral / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D018390:Gene Targeting; D007527:Isoenzymes; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D010587:Phagocytosis
D016207:Cytokines; D007527:Isoenzymes; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II