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Neutrophil extracellular trap formation in the Streptococcus suis-infected cerebrospinal fluid compartment

de Buhr, Nicole; Reuner, Friederike; Neumann, Ariane LU ; Stump-Guthier, Carolin; Tenenbaum, Tobias; Schroten, Horst; Ishikawa, Hiroshi; Müller, Kristin; Beineke, Andreas and Hennig-Pauka, Isabel, et al. (2017) In Cellular microbiology 19(2).
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... (More)

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.

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@article{2976635f-bd80-47f0-bc3a-d8c32dfaec00,
  abstract     = {<p>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.</p>},
  articleno    = {e12649},
  author       = {de Buhr, Nicole and Reuner, Friederike and Neumann, Ariane and Stump-Guthier, Carolin and Tenenbaum, Tobias and Schroten, Horst and Ishikawa, Hiroshi and Müller, Kristin and Beineke, Andreas and Hennig-Pauka, Isabel and Gutsmann, Thomas and Valentin-Weigand, Peter and Baums, Christoph G and von Köckritz-Blickwede, Maren},
  issn         = {1462-5814},
  keyword      = {Animals,Animals, Newborn,Blood-Brain Barrier,Cathelicidins,Cell Culture Techniques,Cerebrospinal Fluid,Deoxyribonucleases,Extracellular Traps,Microbial Viability,Neutrophils,Streptococcal Infections,Streptococcus suis,Swine,Swine Diseases,Journal Article},
  language     = {eng},
  number       = {2},
  publisher    = {Wiley-Blackwell},
  series       = {Cellular microbiology},
  title        = {Neutrophil extracellular trap formation in the Streptococcus suis-infected cerebrospinal fluid compartment},
  url          = {http://dx.doi.org/10.1111/cmi.12649},
  volume       = {19},
  year         = {2017},
}