Interferon-gamma 1b-Induced Gene Expression Alters Neutrophil Function in Patients with Chronic Granulomatous Disease

IFNG decreases incidence of infections in chronic granulomatous disease (CGD) without affecting inability of CGD neutrophils to generate essential microbicidal oxidants. Neutrophil (PMN) function, gene expression, and biochemical parameters were measured off IFN-? and 10-12 hours after 1st and 4th doses of IFN-? administered to nine CGD patients. Non-directed motility and bactericidal activity were increased after treatment with IFN-?; ingestion and O2- generation remained unchanged. Treatment decreased expression of 483 genes and increased 386. Genes (11) associated with PMN activity were upregulated. Genes not routinely associated with neutrophil function were increased including MHCI and II, guanylate binding proteins, and an enzyme synthesizing a NOS cofactor. CD11b expression, f-Actin assembly, and CD 274 antigen were increased after treatment as was NO in PMN lysates. NETs formation after ingestion was increased off IFN-? but moved toward normal after administration. IFN-? provides neutrophils with strategies to compensate for the deficiency found in CGD.