Impaired macrophage function following bacterial stimulation in chronic granulomatous disease.
Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is critical for phagocyte anti-microbial activity and plays a major role in innate immunity. Defects in genes coding for components of the NADPH oxidase enzyme system are responsible for chronic granulomatous disease (CGD), a rare primary neutrophil immunodeficiency associated with recurrent, life-threatening bacterial and fungal infections. Microbial killing and digestion within the neutrophil phagosomal compartment are defective in these patients. NADPH oxidase activity is also crucial for optimal macrophage and dendritic cell function and has recently been implicated in both cross-presentation and T-cell priming. We present evidence of impaired macrophage function in CGD, with attenuated pro-inflammatory cytokine and increased interleukin-10 secretion following bacterial stimulation. These results highlight additional abnormalities in macrophage function associated with CGD and the importance of NADPH oxidase activity in immunity.
Rahman
Farooq Z
FZ
Department of Medicine, University College London, London, WC1E 6BT, UK.
Hayee
Bu'Hussain
B
Chee
Ronnie
R
Segal
Anthony W
AW
Smith
Andrew M
AM
D000942:Antigens, Bacterial / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004789:Enzyme Activation / Q000276:immunology; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D019255:NADPH Oxidases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000276:immunology
D000942:Antigens, Bacterial; D016207:Cytokines; D018836:Inflammation Mediators; D051193:Toll-Like Receptors; D016753:Interleukin-10; D019255:NADPH Oxidases