title: Yersinia enterocolitica-mediated degradation of neutrophil extracellular traps (NETs).
abstract: 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 Ca(2+) and Mg(2+) ions, but not that of a protease inhibitor cocktail, completely abolished NET degradation. We therefore postulate that Y. enterocolitica produces Ca(2+)/Mg(2+)-dependent NET-degrading nucleases as shown for some Gram-positive pathogens.
authors.affiliation: Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Buenteweg 17, 30559 Hannover, Germany.
authors.forename: Helene
authors.initials: H
authors.lastname: Möllerherm
authors.affiliation: Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Buenteweg 17, 30559 Hannover, Germany.
authors.forename: Ariane
authors.initials: A
authors.lastname: Neumann
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, CH-8091 Zurich, Switzerland.
authors.forename: Katrin
authors.initials: K
authors.lastname: Schilcher
authors.affiliation: Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Buenteweg 17, 30559 Hannover, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Blodkamp
authors.affiliation: Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Buenteweg 17, 30559 Hannover, Germany.
authors.forename: Nathalie E
authors.initials: NE
authors.lastname: Zeitouni
authors.affiliation: Helmholtz Centre for Infection Research, D-38124 Braunschweig, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Dersch
authors.affiliation: Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet Stockholm, SE-171-76, Sweden.
authors.forename: Petra
authors.initials: P
authors.lastname: Lüthje
authors.affiliation: Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Buenteweg 17, 30559 Hannover, Germany.
authors.forename: Hassan Y
authors.initials: HY
authors.lastname: Naim
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, CH-8091 Zurich, Switzerland.
authors.forename: Annelies S
authors.initials: AS
authors.lastname: Zinkernagel
authors.affiliation: Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Buenteweg 17, 30559 Hannover, Germany Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, 30559 Hannover, Germany mkoeckbl@tiho-hannover.de.
authors.forename: Maren
authors.initials: M
authors.lastname: von Köckritz-Blickwede
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000737:chemistry / Q000378:metabolism; D065206:Extracellular Traps / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D006801:Humans; D007113:Immunity, Innate; D008274:Magnesium / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D016415:Sequence Alignment; D065288:Serogroup; D015008:Yersinia enterocolitica / Q000145:classification / Q000201:enzymology / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D008565:Membrane Proteins; D004706:Endodeoxyribonucleases; C064668:endA protein, bacteria; D008274:Magnesium; D002118:Calcium
keywords: Gram-negative bacteria; NETosis; host innate immune response