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Chronic granulomatous disease (CGD) is a group of primary immunodeficiencies caused by mutations in genes encoding phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits (gp91phox, p22phox, p47phox, p67phox, and p40phox). CGD phagocytes do not produce reactive oxygen species, kill microbes poorly and consequently patients are susceptible to recurrent life-threatening bacterial and fungal infections. Aspergillus spp. infections, which cause pneumonia and disseminated disease, are the leading cause of death in CGD patients. Up to now it was unclear how neutrophils control Aspergillus species in healthy individuals. We showed for the first time that the microbicidal pathway through neutrophil extracellular traps (NETs) is efficient against A. nidulans conidia and hyphae in vitro, and that restoration of NET formation was achieved by complementation of NADPH oxidase function by gene therapy in a patient with X-linked CGD. This aided clearing severe invasive A. nidulans infection in vivo. We demonstrated the critical role of NET-associate calprotectin for dose-dependent fungistatic of fungicidal anti-Aspergillus activity by Zn2+ sequestration.

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Dr. sc. nat.: PhD on gene therapy for chronic granulomatous disease and neutrophil extracellular traps, University Children´s Hospital Zurich, Switzerland. Research scientist at the Institute of Medical Virology, University of Zurich, Switzerland.

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