Role of Bacterial and Host DNases on Host-Pathogen Interaction during <i>Streptococcus suis</i> Meningitis

Role of Bacterial and Host DNases on Host-Pathogen Interaction during <i>Streptococcus suis</i> Meningitis

<i>Streptococcus</i> <i>suis</i> is a zoonotic agent causing meningitis in pigs and humans. Neutrophils, as the first line of defense against <i>S. suis</i> infections, release neutrophil extracellular traps (NETs) to entrap pathogens. In this study, we investigat...

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Bibliographic Details
Main Authors: Marita 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
Format: Article
Language:English
Published: MDPI AG 2020-07-01
Series:International Journal of Molecular Sciences
Subjects:
Streptococcus suis
meningitis
DNase
neutrophils
NETs
pathogenesis
Online Access:https://www.mdpi.com/1422-0067/21/15/5289
Description
Summary:<i>Streptococcus</i> <i>suis</i> is a zoonotic agent causing meningitis in pigs and humans. Neutrophils, as the first line of defense against <i>S. suis</i> infections, release neutrophil extracellular traps (NETs) to entrap pathogens. In this study, we investigated the role of the secreted nuclease A of <i>S. suis</i> (SsnA) as a NET-evasion factor in vivo and in vitro. Piglets were intranasally infected with <i>S. suis </i>strain<i> </i>10 or an isogenic <i>ssnA</i> mutant. DNase and NET-formation were analyzed in cerebrospinal fluid (CSF) and brain tissue. Animals infected with <i>S. suis </i>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 <i>S. suis</i> by neutrophils, especially when plasma is present. In summary, host nucleases may partially contribute to efficient innate immune response in the CSF.
ISSN:1661-6596
1422-0067

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