Neutrophils Orchestrate the Periodontal Pocket.

Ljubomir Vitkov,Janina Schoen,Christine Schauer,Jasmin Knopf,Bernd Minnich,Luis E Muñoz,Martin Herrmann,Matthias Hannig

doi:10.3389/fimmu.2021.788766

Abstract

The subgingival biofilm attached to tooth surfaces triggers and maintains periodontitis. Previously, late-onset periodontitis has been considered a consequence of dysbiosis and a resultant polymicrobial disruption of host homeostasis. However, a multitude of studies did not show “healthy” oral microbiota pattern, but a high diversity depending on culture, diets, regional differences, age, social state etc. These findings relativise the aetiological role of the dysbiosis in periodontitis. Furthermore, many late-onset periodontitis traits cannot be explained by dysbiosis; e.g. age-relatedness, attenuation by anti-ageing therapy, neutrophil hyper-responsiveness, and microbiota shifting by dysregulated immunity, yet point to the crucial role of dysregulated immunity and neutrophils in particular. Furthermore, patients with neutropenia and neutrophil defects inevitably develop early-onset periodontitis. Intra-gingivally injecting lipopolysaccharide (LPS) alone causes an exaggerated neutrophil response sufficient to precipitate experimental periodontitis. Vice versa to the surplus of LPS, the increased neutrophil responsiveness characteristic for late-onset periodontitis can effectuate gingiva damage likewise. The exaggerated neutrophil extracellular trap (NET) response in late-onset periodontitis is blameable for damage of gingival barrier, its penetration by bacteria and pathogen-associated molecular patterns (PAMPs) as well as stimulation of Th17 cells, resulting in further neutrophil activation. This identifies the dysregulated immunity as the main contributor to periodontal disease.

Highlights

Periodontitis is a collective term for disorders of the tooth supporting tissues with various aetiologies [1]
The crevice is filled with the gingival crevicular fluid (GCF) and is where the periodontal pathogens are initially encountered by the first line of host defence, the crevicular neutrophils and the humoral components of innate and adaptive immunity [8]
The neutrophil hyper-response aims to destroy the pocket pathogens, but they appear to be resistant to neutrophil extracellular traps (NETs) killing [114]

Summary

Introduction

Periodontitis is a collective term for disorders of the tooth supporting tissues with various aetiologies [1]. The most frequently forms of periodontitis can be divided into two main categories triggered by (I) the biofilm attached to the outer tooth surface and (II) by dental pulp necrosis, respectively [1]. The latter is denoted “endodontic-periodontal lesions” [1] and is a subject of endodontology. The subgingival biofilm continuously disperses planktonic bacteria, pathogen-associated molecular patterns (PAMPs), and periodontal pathogenic bacteria [6] These afflict the epithelium in order to get internalised and PAMPs impair the epithelial barrier [7]. Some observations relativise the etiological role of subgingival dysbiosis: (I) the ageassociation of late-onset periodontitis in susceptible individuals and (II) the neutrophil hyper-responsiveness in late-onset periodontitis, (III) the responsiveness of biofilm-induced periodontitis to anti-ageing therapy [11,12,13] and (IV) a microbiota shift by dysregulated immunity [14, 15]

Objectives

Conclusion