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Role of Bacterial and Host DNases on Host-Pathogen Interaction during Streptococcus suis Meningitis.

Abstract
Streptococcus suis is a zoonotic agent causing meningitis in pigs and humans. Neutrophils, as the first line of defense against S. suis infections, release neutrophil extracellular traps (NETs) to entrap pathogens. In this study, we investigated the role of the secreted nuclease A of S. suis (SsnA) as a NET-evasion factor in vivo and in vitro. Piglets were intranasally infected with S. suis strain 10 or an isogenic ssnA mutant. DNase and NET-formation were analyzed in cerebrospinal fluid (CSF) and brain tissue. Animals infected with S. suis strain 10 or S. suis 10ΔssnA showed the presence of NETs in CSF and developed similar clinical signs. Therefore, SsnA does not seem to be a crucial virulence factor that contributes to the development of meningitis in pigs. Importantly, DNase activity was detectable in the CSF of both infection groups, indicating that host nucleases, in contrast to bacterial nuclease SsnA, may play a major role during the onset of meningitis. The effect of DNase 1 on neutrophil functions was further analyzed in a 3D-cell culture model of the porcine blood-CSF barrier. We found that DNase 1 partially contributes to enhanced killing of S. suis by neutrophils, especially when plasma is present. In summary, host nucleases may partially contribute to efficient innate immune response in the CSF.
AuthorsMarita Meurer, Sophie Öhlmann, Marta C Bonilla, Peter Valentin-Weigand, Andreas Beineke, Isabel Hennig-Pauka, Christian Schwerk, Horst Schroten, Christoph G Baums, Maren von Köckritz-Blickwede, Nicole de Buhr
JournalInternational journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 15 (Jul 25 2020) ISSN: 1422-0067 [Electronic] Switzerland
PMID32722502 (Publication Type: Journal Article)
Chemical References
  • Bacterial Proteins
  • Deoxyribonuclease I
Topics
  • Animals
  • Bacterial Proteins (metabolism)
  • Deoxyribonuclease I (metabolism)
  • Meningitis, Bacterial (enzymology, genetics, veterinary)
  • Mutation
  • Neutrophils (enzymology)
  • Streptococcal Infections (enzymology, genetics, veterinary)
  • Streptococcus suis (enzymology, genetics)
  • Swine
  • Swine Diseases (enzymology, genetics)

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