Possible immunomodulatory role of Filifactor alocis through beta-defensin 2 in gingival keratinocytes

Clin Oral Investig. 2024 Nov 27;28(12):658. doi: 10.1007/s00784-024-06043-0.

Abstract

Objectives: The present study aimed to investigate a possible immunomodulatory role of the periodontopathogen Filifactor alocis through the antimicrobial peptide hBD-2 on the expression of chemokines in human gingival keratinocytes.

Materials and methods: Cells were cultured in the presence or absence of periodontopathogenic bacteria, such as F. alocis, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Treponema denticola, to evaluate the regulation of hBD-2, CXCL8 and CCL20. Furthermore, the cells were exposed or not to hBD-2 and the expression of CXCL8 and CCL20 and their receptors was evaluated.

Results: All bacteria induced a significant upregulation of hBD-2, CXCL8, and CCL20 gene expressions. In addition, F. alocis significantly increased their protein levels, as detected by ELISA. Pre-incubation of the cells with the TLR2 inhibitor resulted in a significant downregulation of hBD-2 expression in F. alocis-treated cells. Gingival keratinocytes exposed to hBD-2 resulted in a significant and dose-dependent increase of all chemokines and their receptors.

Conclusions: F. alocis increased the production of chemotactic cytokines, suggesting an increase in the recruitment of immunoinflammatory cells in periodontal diseases. The chemotaxis-promoting effect is partly direct, but is also mediated via hBD-2. F. alocis stimulates the synthesis of hBD-2, which in turn could promote the expression and synthesis of these chemokines and their receptors. In addition, hBD-2 has an autostimulatory effect and stimulates the synthesis of these chemokines, so that the chemotaxis triggered by F. alocis is further fueled.

Clinical relevance: F. alocis and hBD-2 have a significant role in periodontitis, showing their importance for diagnostic and treatment approaches.

Keywords: Beta-defensins; Epithelial cells; Immune response; Inflammation; Periodontitis.

MeSH terms

  • Aggregatibacter actinomycetemcomitans
  • Cells, Cultured
  • Chemokine CCL20* / metabolism
  • Clostridiales
  • Enzyme-Linked Immunosorbent Assay*
  • Gene Expression
  • Gingiva* / cytology
  • Humans
  • Interleukin-8 / metabolism
  • Keratinocytes* / immunology
  • Keratinocytes* / metabolism
  • Porphyromonas gingivalis*
  • Treponema denticola
  • Up-Regulation
  • beta-Defensins* / metabolism

Substances

  • beta-Defensins
  • DEFB4A protein, human
  • Chemokine CCL20
  • Interleukin-8
  • CCL20 protein, human

Supplementary concepts

  • Filifactor alocis