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.
General
Imprint: |
Sudwestdeutscher Verlag Fur Hochschulschriften AG
|
Country of origin: |
United States |
Release date: |
September 2012 |
First published: |
September 2012 |
Authors: |
Matteo Bianchi
|
Dimensions: |
229 x 152 x 9mm (L x W x T) |
Format: |
Paperback - Trade
|
Pages: |
156 |
ISBN-13: |
978-3-8381-3384-3 |
Categories: |
Books >
Science & Mathematics >
Biology, life sciences >
General
|
LSN: |
3-8381-3384-6 |
Barcode: |
9783838133843 |
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