Yersinia enterocolitica-mediated degradation of neutrophil extracellular traps (NETs)

• Published in: FEMS microbiology letters Vol. 362; no. 23; p. fnv192
• Main Authors: Möllerherm, Helene, Neumann, Ariane, Schilcher, Katrin, Blodkamp, Stefanie, Zeitouni, Nathalie E, Dersch, Petra, Lüthje, Petra, Naim, Hassan Y, Zinkernagel, Annelies S, von Köckritz-Blickwede, Maren
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.12.2015
• Subjects: 12-O-Tetradecanoylphorbol-13-acetate; Acetic acid; Amino Acid Sequence; Antimicrobial peptides; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Biodegradation; Blood; Calcium; Calcium - metabolism; Calcium ions; Degradation; Deoxyribonucleic acid; DNA; Endodeoxyribonucleases - chemistry; Endodeoxyribonucleases - metabolism; Entrapment; Extracellular Traps - immunology; Extracellular Traps - metabolism; Extracellular Traps - microbiology; Histones; Humans; Immunity, Innate; Leukocytes (neutrophilic); Magnesium; Magnesium - metabolism; Medicin och hälsovetenskap; Membrane Proteins - chemistry; Membrane Proteins - metabolism; Microbiology; Neutrophils; Neutrophils - immunology; Neutrophils - metabolism; Nuclease; Pathogens; Peptides; Plasmids; Protease inhibitors; Proteinase inhibitors; Sequence Alignment; Serogroup; Serotypes; Yersinia; Yersinia enterocolitica; Yersinia enterocolitica - classification; Yersinia enterocolitica - enzymology; Yersinia enterocolitica - metabolism; host innate immune response; NETosis; Gram-negative bacteria
• ISSN: 1574-6968; 0378-1097; 1574-6968
• DOI: 10.1093/femsle/fnv192

Neutrophil extracellular trap (NET) formation is described as a tool of the innate host defence to fight against invading pathogens. Fibre-like DNA structures associated with proteins such as histones, cell-specific enzymes and antimicrobial peptides are released, thereby entrapping invading pathogens. It has been reported that several bacteria are able to degrade NETs by nucleases and thus evade the NET-mediated entrapment. Here we studied the ability of three different Yersinia serotypes to induce and degrade NETs. We found that the common Yersinia enterocolitica serotypes O:3, O:8 and O:9 were able to induce NETs in human blood-derived neutrophils during the first hour of co-incubation. At later time points, the NET amount was reduced, suggesting that degradation of NETs has occurred. This was confirmed by NET degradation assays with phorbol-myristate-acetate-pre-stimulated neutrophils. In addition, we found that the Yersinia supernatants were able to degrade purified plasmid DNA. The absence of Ca2+ and Mg2+ ions, but not that of a protease inhibitor cocktail, completely abolished NET degradation. We therefore postulate that Y. enterocolitica produces Ca2+/Mg2+-dependent NET-degrading nucleases as shown for some Gram-positive pathogens. This is the first experimental proof that members of the Enterobacteriaceae family are able to degrade NETs, possibly due to a nuclease.