Chronic Granulomatous Disease and Neutrophil Extracellular Traps ab 69.99 € als Taschenbuch: CGD gene therapy and anti-Aspergillus activity of reconstituted NET formation. Aus dem Bereich: Bücher, Wissenschaft, Biologie,
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.
High Quality Content by WIKIPEDIA articles! Chronic granulomatous disease is a diverse group of hereditary diseases in which certain cells of the immune system have difficulty forming the reactive oxygen compounds used to kill certain ingested pathogens. This leads to the formation of granulomata in many organs. CGD affects about 1 in 200,000 people in the United States, with about 20 new cases diagnosed each year. This condition was first discovered in 1954, and in 1957 described as "a fatal granulomatosus of childhood". The underlying cellular mechanism that causes chronic granulomatous disease was discovered in 1967, and research since that time has further elucidated the molecular mechanisms underlying the disease.