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Novel Role of the Antimicrobial Peptide LL-37 in the Protection of Neutrophil Extracellular Traps against Degradation by Bacterial Nucleases

Neumann, Ariane LU ; Voellger, Lena; Berends, Evelien T. M.; Molhoek, E. Margo; Stapels, Daphne A. C.; Midon, Marika; Friaes, Ana; Pingoud, Alfred; Rooijakkers, Suzan H. M. and Gallo, Richard L., et al. (2014) In Journal of Innate Immunity 6(6). p.860-868
Abstract
Neutrophil extracellular traps (NETs) have been described as a fundamental innate immune defence mechanism. They consist of a nuclear DNA backbone associated with different antimicrobial peptides (AMPs) which are able to engulf and kill pathogens. The AMP LL-37, a member of the cathelicidin family, is highly present in NETs. However, the function of LL-37 within NETs is still unknown because it loses its antimicrobial activity when bound to DNA in the NETs. Using immunofluorescence microscopy, we demonstrate that NETs treated with LL-37 are distinctly more resistant to S. aureus nuclease degradation than nontreated NETs. Biochemical assays utilising a random LL-37-fragment library indicated that the blocking effect of LL-37 on nuclease... (More)
Neutrophil extracellular traps (NETs) have been described as a fundamental innate immune defence mechanism. They consist of a nuclear DNA backbone associated with different antimicrobial peptides (AMPs) which are able to engulf and kill pathogens. The AMP LL-37, a member of the cathelicidin family, is highly present in NETs. However, the function of LL-37 within NETs is still unknown because it loses its antimicrobial activity when bound to DNA in the NETs. Using immunofluorescence microscopy, we demonstrate that NETs treated with LL-37 are distinctly more resistant to S. aureus nuclease degradation than nontreated NETs. Biochemical assays utilising a random LL-37-fragment library indicated that the blocking effect of LL-37 on nuclease activity is based on the cationic character of the AMP, which facilitates the binding to neutrophil DNA, thus protecting it from degradation by the nuclease. In good correlation to these data, the cationic AMPs human beta defensin-3 and human neutrophil peptide-1 showed similar protection of neutrophil-derived DNA against nuclease degradation. In conclusion, this study demonstrates a novel role of AMPs in host immune defence: beside its direct antimicrobial activity against various pathogens, cationic AMPs can stabilise neutrophil-derived DNA or NETs against bacterial nuclease degradation. (C) 2014 S. Karger AG, Basel (Less)
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published
subject
keywords
Neutrophil extracellular traps, Antimicrobial peptides, Nucleases, Cathelicidin
in
Journal of Innate Immunity
volume
6
issue
6
pages
860 - 868
publisher
Karger
external identifiers
  • wos:000343642800013
  • scopus:84908645461
ISSN
1662-811X
DOI
10.1159/000363699
language
English
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yes
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8507d65c-30b6-4afe-9f2b-f7b276c66b83 (old id 4783908)
date added to LUP
2014-12-01 07:37:24
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2017-09-19 12:42:53
@article{8507d65c-30b6-4afe-9f2b-f7b276c66b83,
  abstract     = {Neutrophil extracellular traps (NETs) have been described as a fundamental innate immune defence mechanism. They consist of a nuclear DNA backbone associated with different antimicrobial peptides (AMPs) which are able to engulf and kill pathogens. The AMP LL-37, a member of the cathelicidin family, is highly present in NETs. However, the function of LL-37 within NETs is still unknown because it loses its antimicrobial activity when bound to DNA in the NETs. Using immunofluorescence microscopy, we demonstrate that NETs treated with LL-37 are distinctly more resistant to S. aureus nuclease degradation than nontreated NETs. Biochemical assays utilising a random LL-37-fragment library indicated that the blocking effect of LL-37 on nuclease activity is based on the cationic character of the AMP, which facilitates the binding to neutrophil DNA, thus protecting it from degradation by the nuclease. In good correlation to these data, the cationic AMPs human beta defensin-3 and human neutrophil peptide-1 showed similar protection of neutrophil-derived DNA against nuclease degradation. In conclusion, this study demonstrates a novel role of AMPs in host immune defence: beside its direct antimicrobial activity against various pathogens, cationic AMPs can stabilise neutrophil-derived DNA or NETs against bacterial nuclease degradation. (C) 2014 S. Karger AG, Basel},
  author       = {Neumann, Ariane and Voellger, Lena and Berends, Evelien T. M. and Molhoek, E. Margo and Stapels, Daphne A. C. and Midon, Marika and Friaes, Ana and Pingoud, Alfred and Rooijakkers, Suzan H. M. and Gallo, Richard L. and Mörgelin, Matthias and Nizet, Victor and Naim, Hassan Y. and von Koeckritz-Blickwede, Maren},
  issn         = {1662-811X},
  keyword      = {Neutrophil extracellular traps,Antimicrobial peptides,Nucleases,Cathelicidin},
  language     = {eng},
  number       = {6},
  pages        = {860--868},
  publisher    = {Karger},
  series       = {Journal of Innate Immunity},
  title        = {Novel Role of the Antimicrobial Peptide LL-37 in the Protection of Neutrophil Extracellular Traps against Degradation by Bacterial Nucleases},
  url          = {http://dx.doi.org/10.1159/000363699},
  volume       = {6},
  year         = {2014},
}