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Published on: July 1, 2018
Role of Bacterial and Host DNases on Host-Pathogen Interaction during Streptococcus suis Meningitis
Marita Meurer1,2, Sophie Öhlmann3, Marta C Bonilla1,2
1Department of Physiological Chemistry, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
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.
Insights
Streptococcus suis meningitis in piglets was studied. Bacterial nuclease SsnA did not significantly impact meningitis, but host DNase 1 showed potential in enhancing neutrophil defense against S. suis.
Area of Science:
- Veterinary Microbiology
- Immunology
- Bacterial Pathogenesis
Background:
- Streptococcus suis is a zoonotic bacterium causing meningitis in pigs and humans.
- Neutrophils combat S. suis by releasing neutrophil extracellular traps (NETs).
- The role of Streptococcus suis secreted nuclease A (SsnA) in evading NETs was investigated.
Purpose of the Study:
- To determine if SsnA acts as a NET-evasion factor in Streptococcus suis meningitis.
- To investigate the role of host-derived nucleases in the innate immune response to S. suis.
Main Methods:
- Intranasal infection of piglets with S. suis strain 10 or an isogenic ssnA mutant.
- Analysis of DNase activity and NET formation in cerebrospinal fluid (CSF) and brain tissue.
- In vitro 3D cell culture model of the porcine blood-CSF barrier to assess DNase 1 effects on neutrophils.
Main Results:
- Both wild-type S. suis and the ssnA mutant induced NETs in CSF and caused similar clinical signs in piglets.
- Bacterial SsnA was not essential for virulence in this porcine meningitis model.
- DNase activity was detected in CSF from both infection groups, suggesting a role for host nucleases.
- Porcine DNase 1 partially enhanced S. suis killing by neutrophils, particularly in the presence of plasma.
Conclusions:
- Bacterial SsnA is not a critical virulence factor for S. suis meningitis in pigs.
- Host nucleases, such as DNase 1, may play a significant role in the innate immune response within the CSF during S. suis infections.
- Host DNase 1 contributes to enhanced neutrophil-mediated clearance of S. suis.
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