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Am J Respir Cell Mol Biol. 2016 Nov 17. [Epub ahead of print]

Evasion of Neutrophil Extracellular Traps by Respiratory Pathogens.

Author information

  • 1University of Cambridge, Medicine, Cambridge, United Kingdom of Great Britain and Northern Ireland ; dmls2@cam.ac.uk.
  • 2University of Cambridge, 2152, Department of Medicine , Addenbrooke's Hospital , Hills Road , Cambridge, United Kingdom of Great Britain and Northern Ireland , CB2 1TN ; jmp62@cam.ac.uk.
  • 3University of Cambridge, Medicine, Cambridge, United Kingdom of Great Britain and Northern Ireland ; asc32@cam.ac.uk.
  • 4University of Cambridge, 2152, Cambridge, Cambridgeshire, United Kingdom of Great Britain and Northern Ireland.
  • 5Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada ; jj221@cam.ac.uk.
  • 6University of Cambridge, 2152, Cambridge, Cambridgeshire, United Kingdom of Great Britain and Northern Ireland ; an465@medschl.cam.ac.uk.
  • 7University of California, San Diego, La Jolla, California, United States ; vnizet@ucsd.edu.
  • 8University of Cambridge, Medicine, Cambridge, United Kingdom of Great Britain and Northern Ireland ; erc24@cam.ac.uk.

Abstract

The release of neutrophil extracellular traps (NETs) is a major immune mechanism intended to capture pathogens. These histone and protease-coated DNA structures are released by neutrophils in response to a variety of stimuli, including respiratory pathogens, and have been identified in the airways of patients with respiratory infection, cystic fibrosis, acute lung injury, primary graft dysfunction and COPD. NET production has been demonstrated in the lungs of mice infected with Staphylococcus aureus, Klebsiella pneumoniae and Aspergillus fumigatus. Since the discovery of NETs over a decade ago, evidence that "NET evasion" might act as a immune protection strategy among respiratory pathogens including group A Streptococcus, Bordetella pertussis, and Haemophilus influenzae has been growing, with the majority of these studies being published in the past two years. Evasion strategies fall into three main categories: inhibition of NETs release by down-regulating host inflammatory responses, degradation of NETs using pathogen-derived deoxyribonucleases, and resistance to the microbicidal components of NETs, which involves a variety of mechanisms including encapsulation. Hence, the evasion of NETs appears to be a widespread strategy to allow pathogen proliferation and dissemination, and is currently a topic of intense research interest. This article will outline the evidence supporting the three main strategies of NET evasion: inhibition, degradation, and resistance, with particular reference to common respiratory pathogens.

KEYWORDS:

Deoxyribonuclease; Neutrophil extracellular traps; Streptococcus; immune evasion

PMID:
27854516
DOI:
10.1165/rcmb.2016-0193PS
[PubMed - as supplied by publisher]
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