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

Marita Meurer,Isabel Hennig-Pauka,Nicole De Buhr,Christian Schwerk,Marta C Bonilla,Andreas Beineke,Peter Valentin-Weigand,Sophie Öhlmann,Horst Schroten,Maren Von Köckritz-Blickwede,Christoph G Baums

doi:10.3390/ijms21155289

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.

Highlights

Bacterial meningitis is a life-threatening disease [1] in humans and pigs that can be caused by Streptococcus suis [2,3]
The DNase SsnA is known as a major neutrophil extracellular traps (NETs)-evasion factor of S. suis [10]
The aim of our study was to investigate the role of the bacterial nuclease SsnA and the host DNase 1 during S. suis meningitis in vivo and in vitro

Summary

Introduction

Bacterial meningitis is a life-threatening disease [1] in humans and pigs that can be caused by Streptococcus suis [2,3]. Neutrophils are the major immune cell inside the cerebrospinal fluid (CSF) during bacterial meningitis [4]. The host itself is known to produce DNases to recycle NET-structures and to avoid tissue-damaging effects of NETs during infectious or non-infectious diseases [6,7,8]. Various bacteria have evolved DNases as NET-evasion factors to escape from NET-entrapment and killing. For S. suis two NET-evading nucleases have been described: EndAsuis and SsnA. The membrane-anchored EndAsuis only contributes to NET-evasion. The released SsnA has been shown to efficiently reduce antimicrobial effects of NETs to improve survival of S. suis in the presence of NETs [9,10]. SsnA is active in CSF during S. suis meningitis [2]. The question of whether SsnA contributes to the development of meningitis in piglets as the natural host in vivo has not been investigated so far

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