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

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Author

  • Angela Pizzolla
  • Malin Hultqvist
  • Bo Nilson
  • Melissa J. Grimm
  • Tove Eneljung
  • Ing-Marie Jonsson
  • Margareta Verdrengh
  • Tiina Kelkka
  • Inger Gjertsson
  • Brahm H. Segal
  • Rikard Holmdahl
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Summary, in English

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.

Department/s

Publishing year

2012

Language

English

Pages

5003-5011

Publication/Series

Journal of Immunology

Volume

188

Issue

10

Document type

Journal article

Publisher

American Association of Immunologists

Topic

  • Immunology in the medical area

Status

Published

Research group

  • Immunology

ISBN/ISSN/Other

  • ISSN: 1550-6606