Proinflammatory cytokine response toward fungi but not bacteria in chronic granulomatous disease

To determine a role for the NADPH oxidase activity in monocyte and neutrophil cytokine responses toward bacterial and fungal pathogens, we analyzed 10 patients with CGD with previously described mutations in genes encoding for either the cytosolic NADPH oxidase proteins, that is, p47phox or p67phox, or the membrane-expressed cytochrome-b558 subunit gp91phox, all resulting in a failure to produce ROS (see Table E1 in this article's Online Repository at www.jacionline.org).1 The role of 2 known signaling pathways involved in bacterial and fungal host defense was determined in patients deficient in caspase recruitment domain-containing protein 9 (CARD9)- and IL-1 receptor-associated kinase 4 (IRAK4). [...]we have demonstrated that monocytes and neutrophils from patients with CGD show an exacerbated proinflammatory response to intact fungal but not to bacterial pathogens.\n Control subjects originated from the same hospital as the patients.