Phenotype of mice and macrophages deficient in both phagocyte oxidase and inducible nitric oxide synthase

The two genetically established antimicrobial mechanisms of macrophages are production of reactive oxygen intermediates by phagocyte oxidase (phox) an d reactive nitrogen intermediates by inducible nitric oxide synthase (NOS2) . Mice doubly deficient in both enzymes (gp91(phox-/-)/NOS2(-/-)) formed ma ssive abscesses containing commensal organisms, mostly enteric bacteria, ev en when reared under specific pathogen-free conditions with antibiotics. Ne ither parental strain showed such infections. Thus, phox and NOS2 appear to compensate for each other's deficiency in providing resistance to indigeno us bacteria, and no other pathway does so fully. Macrophages from gp91(phox -/-) NOS2(-/-)mice could not kill virulent Listeria. Their killing of S. ty phimurium, E. coli, and attenuated Listeria was markedly diminished but dem onstrable, establishing the existence of a mechanism of macrophage antibact erial activity independent of phox and NOS2.