title: Neutrophil extracellular trap formation in the Streptococcus suis-infected cerebrospinal fluid compartment.
abstract: Streptococcus suis is an important meningitis-causing pathogen in pigs and humans. Neutrophil extracellular traps (NETs) have been identified as host defense mechanism against different pathogens. Here, NETs were detected in the cerebrospinal fluid (CSF) of S. suis-infected piglets despite the presence of active nucleases. To study NET-formation and NET-degradation after transmigration of S. suis and neutrophils through the choroid plexus epithelial cell barrier, a previously described model of the human blood-CSF barrier was used. NETs and respective entrapment of streptococci were recorded in the "CSF compartment" despite the presence of active nucleases. Comparative analysis of S. suis wildtype and different S. suis nuclease mutants did not reveal significant differences in NET-formation or bacterial survival. Interestingly, transcript expression of the human cathelicidin LL-37, a NET-stabilizing factor, increased after transmigration of neutrophils through the choroid plexus epithelial cell barrier. In good accordance, the porcine cathelicidin PR-39 was significantly increased in CSF of piglets with meningitis. Furthermore, we confirmed that PR-39 is associated with NETs in infected CSF and inhibits neutrophil DNA degradation by bacterial nucleases. In conclusion, neutrophils form NETs after breaching the infected choroid plexus epithelium, and those NETs may be protected by antimicrobial peptides against bacterial nucleases.
authors.affiliation: Department of Physiological Chemistry, Department of Infectious Diseases, University of Veterinary Medicine Hannover, Hannover, Germany.|Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Hannover, Germany.|Institute for Microbiology, Department of Infectious Diseases, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: de Buhr
authors.affiliation: Department of Physiological Chemistry, Department of Infectious Diseases, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Reuner
authors.affiliation: Department of Physiological Chemistry, Department of Infectious Diseases, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Ariane
authors.initials: A
authors.lastname: Neumann
authors.affiliation: Department of Pediatrics, Pediatric Infectious Diseases, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Stump-Guthier
authors.affiliation: Department of Pediatrics, Pediatric Infectious Diseases, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Tenenbaum
authors.affiliation: Department of Pediatrics, Pediatric Infectious Diseases, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Schroten
authors.affiliation: Department of NDU Life Sciences, School of Life Dentistry at Tokyo, The Nippon Dental University, Chiyoda-ku, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishikawa
authors.affiliation: Institute for Veterinary Pathology, Faculty of Veterinary Medicine, University Leipzig, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Müller
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Beineke
authors.affiliation: University Clinic for Swine, University of Veterinary Medicine Vienna, Vienna, Austria.
authors.forename: Isabel
authors.initials: I
authors.lastname: Hennig-Pauka
authors.affiliation: Research group Biophysics, Research Centre Borstel, Borstel, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gutsmann
authors.affiliation: Institute for Microbiology, Department of Infectious Diseases, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Valentin-Weigand
authors.affiliation: Institute for Bacteriology and Mycology, Centre for Infectious Diseases, Faculty of Veterinary Medicine, University Leipzig, Germany.
authors.forename: Christoph G
authors.initials: CG
authors.lastname: Baums
authors.affiliation: Department of Physiological Chemistry, Department of Infectious Diseases, University of Veterinary Medicine Hannover, Hannover, Germany.|Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: von Köckritz-Blickwede
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001812:Blood-Brain Barrier; D054804:Cathelicidins / Q000032:analysis; D018929:Cell Culture Techniques; D002555:Cerebrospinal Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology* / Q000382:microbiology*; D003851:Deoxyribonucleases / Q000172:deficiency / Q000378:metabolism; D065206:Extracellular Traps / Q000276:immunology*; D050296:Microbial Viability; D009504:Neutrophils / Q000276:immunology*; D013290:Streptococcal Infections / Q000276:immunology / Q000473:pathology / Q000662:veterinary*; D017011:Streptococcus suis / Q000276:immunology*; D013552:Swine; D013553:Swine Diseases / Q000276:immunology / Q000473:pathology*
chemical_list: D054804:Cathelicidins; D003851:Deoxyribonucleases