Neutrophils Orchestrate the Periodontal Pocket

Front Immunol. 2021 Nov 24:12:788766. doi: 10.3389/fimmu.2021.788766. eCollection 2021.

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.

Keywords: NET formation; bacterial membrane vesicles; caspase 11; caspase 4; dysbiosis; dysregulated immunity; outer membrane vesicles.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bacteria / growth & development
  • Bacteria / immunology*
  • Bacteria / pathogenicity
  • Biofilms / growth & development
  • Dysbiosis
  • Extracellular Traps / immunology*
  • Extracellular Traps / metabolism
  • Extracellular Traps / microbiology
  • Gingiva / immunology*
  • Gingiva / metabolism
  • Gingiva / microbiology
  • Gingiva / pathology
  • Humans
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism
  • Neutrophil Activation*
  • Neutrophils / immunology*
  • Neutrophils / metabolism
  • Neutrophils / microbiology
  • Pathogen-Associated Molecular Pattern Molecules / metabolism
  • Periodontal Pocket / immunology*
  • Periodontal Pocket / metabolism
  • Periodontal Pocket / microbiology
  • Periodontal Pocket / pathology
  • Periodontitis / immunology*
  • Periodontitis / metabolism
  • Periodontitis / microbiology
  • Periodontitis / pathology
  • Signal Transduction

Substances

  • Inflammation Mediators
  • Pathogen-Associated Molecular Pattern Molecules