Neutrophils Orchestrate the Periodontal Pocket

• Published in: Frontiers in immunology 2021-11, Vol.12, p.788766-788766
• Main Authors: Vitkov, Ljubomir, Muñoz, Luis E, Schoen, Janina, Knopf, Jasmin, Schauer, Christine, Minnich, Bernd, Herrmann, Martin, Hannig, Matthias
• Format: Article
• Language: English
• Subjects: Animals; Bacteria - growth & development; Bacteria - immunology; Bacteria - pathogenicity; bacterial membrane vesicles; Biofilms - growth & development; caspase 11; caspase 4; Dysbiosis; dysregulated immunity; Extracellular Traps - immunology; Extracellular Traps - metabolism; Extracellular Traps - microbiology; Gingiva - immunology; Gingiva - metabolism; Gingiva - microbiology; Gingiva - pathology; Humans; Immunology; Inflammation Mediators - immunology; Inflammation Mediators - metabolism; NET formation; 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
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.788766

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.