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Reactive Oxygen Species Produced by the NADPH Oxidase 2 Complex in Monocytes Protect Mice from Bacterial Infections

Pizzolla, Angela; Hultqvist, Malin LU ; Nilson, Bo LU ; Grimm, Melissa J.; Eneljung, Tove; Jonsson, Ing-Marie; Verdrengh, Margareta; Kelkka, Tiina; Gjertsson, Inger and Segal, Brahm H., et al. (2012) In Journal of Immunology 188(10). p.5003-5011
Abstract
Chronic granulomatous disease (CGD) is an inherited disorder characterized by recurrent life-threatening bacterial and fungal infections. CGD results from defective production of reactive oxygen species by phagocytes caused by mutations in genes encoding the NADPH oxidase 2 (NOX2) complex subunits. Mice with a spontaneous mutation in Ncf1, which encodes the NCF1 (p47(Phox)) subunit of NOX2, have defective phagocyte NOX2 activity. These mice occasionally develop local spontaneous infections by Staphylococcus xylosus or by the common CGD pathogen Staphylococcus aureus. Ncf1 mutant mice were more susceptible to systemic challenge with these bacteria than were wild-type mice. Transgenic Ncf1 mutant mice harboring the wild-type Ncf1 gene under... (More)
Chronic granulomatous disease (CGD) is an inherited disorder characterized by recurrent life-threatening bacterial and fungal infections. CGD results from defective production of reactive oxygen species by phagocytes caused by mutations in genes encoding the NADPH oxidase 2 (NOX2) complex subunits. Mice with a spontaneous mutation in Ncf1, which encodes the NCF1 (p47(Phox)) subunit of NOX2, have defective phagocyte NOX2 activity. These mice occasionally develop local spontaneous infections by Staphylococcus xylosus or by the common CGD pathogen Staphylococcus aureus. Ncf1 mutant mice were more susceptible to systemic challenge with these bacteria than were wild-type mice. Transgenic Ncf1 mutant mice harboring the wild-type Ncf1 gene under the human CD68 promoter (MN+ mice) gained the expression of NCF1 and functional NOX2 activity specifically in monocytes/macrophages, although minimal NOX2 activity was also detected in some CD11b(+)Ly6G(+) cells defined as neutrophils. MN+ mice did not develop spontaneous infection and were more resistant to administered staphylococcal infections compared with MN- mice. Most strikingly, MN+ mice survived after being administered Burkholderia cepacia, an opportunistic pathogen in CGD patients, whereas MN- mice died. Thus, monocyte/macrophage expression of functional NCF1 protected against spontaneous and administered bacterial infections. The Journal of Immunology, 2012, 188: 5003-5011. (Less)
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Journal of Immunology
volume
188
issue
10
pages
5003 - 5011
publisher
American Association of Immunologists
external identifiers
  • wos:000303634300033
  • scopus:84861164816
ISSN
1550-6606
DOI
10.4049/jimmunol.1103430
language
English
LU publication?
yes
id
402edd80-e25d-418f-b7d9-ff325123d859 (old id 2826533)
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2012-07-03 10:26:25
date last changed
2017-09-24 03:55:32
@article{402edd80-e25d-418f-b7d9-ff325123d859,
  abstract     = {Chronic granulomatous disease (CGD) is an inherited disorder characterized by recurrent life-threatening bacterial and fungal infections. CGD results from defective production of reactive oxygen species by phagocytes caused by mutations in genes encoding the NADPH oxidase 2 (NOX2) complex subunits. Mice with a spontaneous mutation in Ncf1, which encodes the NCF1 (p47(Phox)) subunit of NOX2, have defective phagocyte NOX2 activity. These mice occasionally develop local spontaneous infections by Staphylococcus xylosus or by the common CGD pathogen Staphylococcus aureus. Ncf1 mutant mice were more susceptible to systemic challenge with these bacteria than were wild-type mice. Transgenic Ncf1 mutant mice harboring the wild-type Ncf1 gene under the human CD68 promoter (MN+ mice) gained the expression of NCF1 and functional NOX2 activity specifically in monocytes/macrophages, although minimal NOX2 activity was also detected in some CD11b(+)Ly6G(+) cells defined as neutrophils. MN+ mice did not develop spontaneous infection and were more resistant to administered staphylococcal infections compared with MN- mice. Most strikingly, MN+ mice survived after being administered Burkholderia cepacia, an opportunistic pathogen in CGD patients, whereas MN- mice died. Thus, monocyte/macrophage expression of functional NCF1 protected against spontaneous and administered bacterial infections. The Journal of Immunology, 2012, 188: 5003-5011.},
  author       = {Pizzolla, Angela and Hultqvist, Malin and Nilson, Bo and Grimm, Melissa J. and Eneljung, Tove and Jonsson, Ing-Marie and Verdrengh, Margareta and Kelkka, Tiina and Gjertsson, Inger and Segal, Brahm H. and Holmdahl, Rikard},
  issn         = {1550-6606},
  language     = {eng},
  number       = {10},
  pages        = {5003--5011},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {Reactive Oxygen Species Produced by the NADPH Oxidase 2 Complex in Monocytes Protect Mice from Bacterial Infections},
  url          = {http://dx.doi.org/10.4049/jimmunol.1103430},
  volume       = {188},
  year         = {2012},
}