Mini Review ARTICLE

Front. Immunol., 01 March 2013 | http://dx.doi.org/10.3389/fimmu.2013.00045

NETosis and NADPH oxidase: at the intersection of host defense, inflammation, and injury

  • 1Division of Infectious Diseases, Department of Medicine, University at Buffalo School of Medicine, Buffalo, NY, USA
  • 2Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA
  • 3Department of Anesthesiology, University at Buffalo School of Medicine, Buffalo, NY, USA
  • 4Department of Pathology and Anatomical Sciences, University at Buffalo School of Medicine, Buffalo, NY, USA
  • 5Veterans Administration of Western New York Healthcare System, Buffalo, NY, USA
  • 6Laboratory for Molecular Infection Medicine Sweden, Department of Clinical Microbiology, Umeå University, Umeå, Sweden
  • 7Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY, USA

Neutrophils are armed with both oxidant-dependent and -independent pathways for killing pathogens. Activation of the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase constitutes an emergency response to infectious threat and results in the generation of antimicrobial reactive oxidants. In addition, NADPH oxidase activation in neutrophils is linked to activation of granular proteases and generation of neutrophil extracellular traps (NETs). NETosis involves the release of nuclear and granular components that can target extracellular pathogens. NETosis is activated during microbial threat and in certain conditions mimicking sepsis, and can result in both augmented host defense and inflammatory injury. In contrast, apoptosis, the physiological form of neutrophil death, not only leads to non-inflammatory cell death but also contributes to alleviate inflammation. Although there are significant gaps in knowledge regarding the specific contribution of NETs to host defense, we speculate that the coordinated activation of NADPH oxidase and NETosis maximizes microbial killing. Work in engineered mice and limited patient experience point to varying susceptibility of bacterial and fungal pathogens to NADPH oxidase versus NET constituents. Since reactive oxidants and NET constituents can injure host tissue, it is important that these pathways be tightly regulated. Recent work supports a role for NETosis in both acute lung injury and in autoimmunity. Knowledge gained about mechanisms that modulate NETosis may lead to novel therapeutic approaches to limit inflammation-associated injury.

Keywords: NETs, NADPH oxidase, neutrophils, inflammation, injury

Citation: Almyroudis NG, Grimm MJ, Davidson BA, Röhm M, Urban CF and Segal BH (2013) NETosis and NADPH oxidase: at the intersection of host defense, inflammation, and injury. Front. Immunol. 4:45. doi: 10.3389/fimmu.2013.00045

Received: 18 December 2012; Accepted: 07 February 2013;
Published online: 01 March 2013.

Edited by:

Marko Radic, University of Tennessee, USA

Reviewed by:

Heather Parker, University of Otago, Christchurch, New Zealand
Jinfang Ma, Johns Hopkins University, USA

Copyright: © 2013 Almyroudis, Grimm, Davidson, Röhm, Urban and Segal. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

*Correspondence: Brahm H. Segal, Division of Infectious Diseases, Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA. e-mail: brahm.segal@roswellpark.org