Abstract

ABSTRACT Oral innate immunity is led by neutrophils. It is still unclear how their main antimicrobial mechanisms against different biofilms may contribute to balance or dysregulation in the oral cavity. We investigated the capacity of commensal (Streptococcus oralis) and pathogenic (Porphyromonas gingivalis or Aggregatibacter actinomycetemcomitans) monospecies biofilms to induce or to inhibit selected antimicrobial mechanisms of neutrophils. S. oralis induced neutrophil extracellular traps (NETs) formation, reactive oxygen species (ROS) production, and matrix metalloproteinases (MMPs) 8 and 9 secretion. However, these responses were partially reduced in PMA-activated neutrophils indicating a balance-like neutrophil response, which might be important for the maintenance of oral health. P. gingivalis generally induced ROS. Reduced NET formation and significantly decreased MMP secretion were detectable in activated neutrophils highlighting P. gingivalis’ nucleolytic and proteolytic activity, which might support bacterial colonization and pathogenesis of periodontitis. In contrast, A. actinomycetemcomitans did not affect the levels of antimicrobial factors in activated neutrophils and induced NET formation, ROS production, and secretion of MMP-8 and -9 in neutrophils alone, which might contribute to tissue destruction and disease progression. In summary, neutrophil responses to biofilms were species-specific and might support either maintenance of oral health or pathogenesis of periodontitis depending on the species.

Highlights

  • The oral microbiome consists of several hundred different bacterial species [1,2,3,4]

  • The isolated human neutrophils were incubated with the different monospecies biofilms (S. oralis, A. actinomycetemcomitans, and P. gingivalis) for 3.5 h

  • Neutrophils were activated with the pro­ tein kinase C activator phorbol 12-myristate 13-acetate (PMA), which is a widely used experimental substance to efficiently stimulate various neutrophil reactions, such as reactive oxygen species (ROS) production, NETosis, apoptosis, or degranulation [56,57,58]

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Summary

Introduction

The oral microbiome consists of several hundred different bacterial species [1,2,3,4]. These are able to form three-dimensional structures with an extracel­ lular polymeric matrix, known as ‘biofilms’ [3,4,5,6]. The oral healthassociated multispecies biofilm consists mostly of Streptococcus spp. and Actinomyces spp., where Streptococcus oralis dominate the early formation stage [10,11,12]. Until 2018, period­ ontitis was divided into an aggressive and a chronic form, among others. Both forms are combined under a single category. Periodontitis is defined on the basis of a stage and grade system, while ‘grade’

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