Phagocyte NADPH oxidase, chronic granulomatous disease and mycobacterial infections

2014 ◽  
Vol 16 (8) ◽  
pp. 1168-1178 ◽  
Author(s):  
Christine Deffert ◽  
Julien Cachat ◽  
Karl-Heinz Krause
Keyword(s):  
Nadph Oxidase ◽  
Chronic Granulomatous Disease ◽  
Granulomatous Disease ◽  
Mycobacterial Infections ◽  
Phagocyte Nadph Oxidase

scholarly journals Staphylococcus aureus, phagocyte NADPH oxidase and chronic granulomatous disease

2016 ◽  
pp. fuw042 ◽  
Author(s):  
Helene Buvelot ◽  
Klara M. Posfay-Barbe ◽  
Patrick Linder ◽  
Jacques Schrenzel ◽  
Karl-Heinz Krause
Keyword(s):  
Staphylococcus Aureus ◽  
Nadph Oxidase ◽  
Chronic Granulomatous Disease ◽  
Granulomatous Disease ◽  
Phagocyte Nadph Oxidase

scholarly journals The p47phox mouse knock-out model of chronic granulomatous disease.

1995 ◽  
Vol 182 (3) ◽  
pp. 751-758 ◽  
Author(s):  
S H Jackson ◽  
J I Gallin ◽  
S M Holland
Keyword(s):  
Nadph Oxidase ◽  
Chronic Granulomatous Disease ◽  
Fungal Infections ◽  
Critical Role ◽  
Granulomatous Inflammation ◽  
Mammalian Host ◽  
Granulomatous Disease ◽  
Knock Out ◽  
Phagocyte Nadph Oxidase ◽  
Life Threatening

Chronic granulomatous disease (CGD) is caused by a congenital defect in phagocyte reduced nicotinamide dinucleotide phosphate (NADPH) oxidase production of superoxide and related species. It is characterized by recurrent life-threatening bacterial and fungal infections and tissue granuloma formation. We have created a mouse model of CGD by targeted disruption of p47phox, one of the genes in which mutations cause human CGD. Identical to the case in human CGD, leukocytes from p47phox-/- mice produced no superoxide and killed staphylococci ineffectively. p47phox-/- mice developed lethal infections and granulomatous inflammation similar to those encountered in human CGD patients. This model mirrors human CGD and confirms a critical role for the phagocyte NADPH oxidase in mammalian host defense.

scholarly journals Unusual late presentation of X-linked chronic granulomatous disease in an adult female with a somatic mosaic for a novel mutation in CYBB

Blood ◽  
2005 ◽  
Vol 105 (1) ◽  
pp. 61-66 ◽  
Author(s):  
Baruch Wolach ◽  
Yitshak Scharf ◽  
Ronit Gavrieli ◽  
Martin de Boer ◽  
Dirk Roos
Keyword(s):  
Nadph Oxidase ◽  
Chronic Granulomatous Disease ◽  
X Chromosome ◽  
Clinical Symptoms ◽  
Novel Mutation ◽  
Late Presentation ◽  
Granulomatous Disease ◽  
Phagocyte Nadph Oxidase ◽  
Mucosal Cells ◽  
General Defect

Abstract Most patients with chronic granulomatous disease (CGD) have mutations in the X-linked CYBB gene that encodes gp91phox, a component of the phagocyte NADPH oxidase. The resulting X-linked form of CGD is usually manifested in boys. Rarely, X-CGD is encountered in female carriers with extreme expression of the mutated gene. Here, we report on a woman with a novel mutation in CYBB (CCG[90-92] → GGT), predicting Tyr30Arg31 → stop, Val in gp91phox, who presented with clinical symptoms at the age of 66. The mutation was present in heterozygous form in genomic DNA from her leukocytes but was fully expressed in mRNA from these cells, indicating that in her leukocytes the X chromosome carrying the nonmutated CYBB allele had been inactivated. Indeed, only 0.4% to 2% of her neutrophils showed NADPH oxidase activity. This extreme skewing of her X-chromosome inactivation was not found in her cheek mucosal cells and is thus not due to a general defect in gene methylation on one X chromosome. Moreover, the CYBB mutation was not present in the DNA from her cheek cells and was barely detectable in the DNA from her memory T lymphocytes. Thus, this patient shows a somatic mosaic for the CYBB mutation, which probably originated during her lifetime in her bone marrow.

scholarly journals Hyperinflammation in chronic granulomatous disease and anti-inflammatory role of the phagocyte NADPH oxidase

2008 ◽  
Vol 30 (3) ◽  
pp. 255-271 ◽  
Author(s):  
Michela G. Schäppi ◽  
Vincent Jaquet ◽  
Dominique C. Belli ◽  
Karl-Heinz Krause
Keyword(s):  
Nadph Oxidase ◽  
Chronic Granulomatous Disease ◽  
Granulomatous Disease ◽  
Phagocyte Nadph Oxidase ◽  
Anti Inflammatory

Chronic granulomatous disease caused by mutations other than the common GT deletion inNCF1, the gene encoding the p47phoxcomponent of the phagocyte NADPH oxidase

2006 ◽  
Vol 27 (12) ◽  
pp. 1218-1229 ◽  
Author(s):  
Dirk Roos ◽  
Martin de Boer ◽  
M. Yavuz Köker ◽  
Jan Dekker ◽  
Vinita Singh-Gupta ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Chronic Granulomatous Disease ◽  
Granulomatous Disease ◽  
Gene Encoding ◽  
Phagocyte Nadph Oxidase ◽  
The Common

EROS is required for phagocyte NADPH oxidase function in humans and its deficiency causes Chronic Granulomatous Disease

2018 ◽  
Author(s):  
David C. Thomas ◽  
Louis-Marie Charbonnier ◽  
Andrea Schejtman ◽  
Hasan Aldhekri ◽  
Eve Coomber ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Chronic Granulomatous Disease ◽  
Respiratory Burst ◽  
Reactive Oxygen ◽  
Human Cells ◽  
List Type ◽  
Oxygen Species ◽  
Granulomatous Disease ◽  
Phagocyte Nadph Oxidase

AbstractThe phagocyte respiratory burst is mediated by the phagocyte NADPH oxidase, a multi-protein subunit complex that facilitates production of reactive oxygen species and which is essential for host defence. Monogenic deficiency of individual subunits leads to chronic granulomatous disease (CGD), which is characterized by an inability to make reactive oxygen species, leading to severe opportunistic infections and auto-inflammation. However, not all cases of CGD are due to mutations in previously identified subunits. We recently showed that Eros, a novel and highly conserved ER-resident transmembrane protein, is essential for the phagocyte respiratory burst in mice because it is required for expression of gp91phox-p22phox heterodimer, which are the membrane bound components of the phagocyte NADPH oxidase. We now show that the function of EROS is conserved in human cells and describe a case of CGD secondary to a homozygous EROS mutation that abolishes EROS protein expression. This work demonstrates the fundamental importance of EROS in human immunity and describes a novel cause of CGD.Clinical ImplicationsChronic granulomatous disease is caused by an inability to make reactive oxygen species via the phagocyte NADPH oxidase. Mutations in C17ORF62/EROS, which controls gp91phox- p22phox abundance, are a novel cause of chronic granulomatous disease.Key MessagesThe murine gene, Eros, is known to regulate abundance of gp91phox-p22phox heterodimer and Eros deficient mice are susceptible to infectionWe show that the function of EROS is conserved in human cells and that a homozygous mutation in EROS causes chronic granulomatous disease

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