The antimicrobial peptide LL-37 stabilizes neutrophil extracellular traps against Staphylococcus areus nuclease degradation

Neutrophil extracellular traps (NETS) have been identified as a novel important host innate immune defence mechanism against bacterial pathogens e.g. Staphylococcus areus. Thes NETs consist of a nuclear DNA backbone associated with different antimicrobial peptides (AMPs), which are able to engulf the pathogens and kill them with decorated proteins. The AMP LL-37, a member of the cathelicidin family, is highly present in NETs. However, the function of LL-37 within the NETs is still unknown, since LL-37 loses its antimicrobial acitivity when bound to DNA in the NETs.

Using immunofluorescence microscopy we could demonstrate that NETs treated with LL-37 were distinctly more resistant to S. areus nuclease degradation as compared to non-treated NETs. Biochemical assays utilizing a random LL-37 fragment library indicate 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 (hBD3) and human neutrophil peptide-1 (HNP-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. Besides its direct antimicrobial activity against various pathogens, cationic AMPs can stabilize neutrophil-derived DNA or NETs against staphylococcal nuclease degradation.