Header

UZH-Logo

Maintenance Infos

Restoration of NET formation by gene therapy in CGD controls aspergillosis


Bianchi, M; Hakkim, A; Brinkmann, V; Siler, U; Seger, R A; Zychlinsky, A; Reichenbach, J (2009). Restoration of NET formation by gene therapy in CGD controls aspergillosis. Blood, 114(13):2619-2622.

Abstract

Chronic granulomatous disease (CGD) patients have impaired nicotinamide adenine dinucleotide phosphate (NADPH) oxidase function, resulting in poor antimicrobial activity of neutrophils, including the inability to generate neutrophil extracellular traps (NETs). Invasive aspergillosis is the leading cause of death in patients with CGD; it is unclear how neutrophils control Aspergillus species in healthy persons. The aim of this study was to determine whether gene therapy restores NET formation in CGD by complementation of NADPH oxidase function, and whether NETs have antimicrobial activity against Aspergillus nidulans. Here we show that reconstitution of NET formation by gene therapy in a patient with CGD restores neutrophil elimination of A nidulans conidia and hyphae and is associated with rapid cure of preexisting therapy refractory invasive pulmonary aspergillosis, underlining the role of functional NADPH oxidase in NET formation and antifungal activity.

Abstract

Chronic granulomatous disease (CGD) patients have impaired nicotinamide adenine dinucleotide phosphate (NADPH) oxidase function, resulting in poor antimicrobial activity of neutrophils, including the inability to generate neutrophil extracellular traps (NETs). Invasive aspergillosis is the leading cause of death in patients with CGD; it is unclear how neutrophils control Aspergillus species in healthy persons. The aim of this study was to determine whether gene therapy restores NET formation in CGD by complementation of NADPH oxidase function, and whether NETs have antimicrobial activity against Aspergillus nidulans. Here we show that reconstitution of NET formation by gene therapy in a patient with CGD restores neutrophil elimination of A nidulans conidia and hyphae and is associated with rapid cure of preexisting therapy refractory invasive pulmonary aspergillosis, underlining the role of functional NADPH oxidase in NET formation and antifungal activity.

Statistics

Citations

230 citations in Web of Science®
240 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

142 downloads since deposited on 01 Feb 2010
31 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2009
Deposited On:01 Feb 2010 10:56
Last Modified:03 Aug 2017 15:12
Publisher:American Society of Hematology
ISSN:0006-4971
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1182/blood-2009-05-221606
PubMed ID:19541821

Download

Preview Icon on Download
Preview
Filetype: PDF
Size: 1MB
View at publisher