Activation of RANKL-induced osteoclasts and memory T lymphocytes by Porphyromonas gingivalis is serotype dependant

J Clin Periodontol. 2014 May;41(5):451-9. doi: 10.1111/jcpe.12236.

Abstract

Aim: Destructive periodontitis is associated with a Th1-Th17 immune response and activation of RANKL-induced osteoclasts. In addition, Porphyromonas gingivalis K1 and K2 serotypes induce a strong Th1-Th17 response. This study aimed to investigate whether these P. gingivalis serotypes induce higher osteoclasts activation, by increased Th17-associated RANKL production, and an antigen-specific memory T-lymphocyte response.

Material and methods: The RANKL production and TRAP(+) osteoclast induction were quantified on naïve T lymphocytes stimulated with dendritic cells primed with the P. gingivalis serotypes. The T-bet, GATA-3, RORC2 and Foxp3 expression was correlated with RANKL production. The frequency of proliferating memory T lymphocytes in response to P. gingivalis serotypes was determined in both periodontitis and healthy subjects.

Results: T lymphocytes stimulated by K1 or K2-primed dendritic cells elicited higher levels of RANKL and TRAP(+) osteoclasts than cells stimulated with the other serotypes. RANKL positively correlated with RORC2. Whereas periodontitis patients had a higher frequency of memory T lymphocytes responding to K1 or K2, healthy subjects had a higher frequency of memory T lymphocytes responding to K4 or K(-) .

Conclusions: P. gingivalis serotypes K1 and K2, but not others, are associated with an increased production of the osteoclastogenesis-related factor RANKL. This important information suggests that these serotypes could elicit a greater bone resorption in vivo and have a role in the periodontitis pathogenesis.

Keywords: Porphyromonas gingivalis; RANKL; T lymphocytes; bone resorption; periodontitis; serotypes.

Publication types

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

MeSH terms

  • Acid Phosphatase / analysis
  • Acid Phosphatase / immunology
  • Animals
  • Antigens, Bacterial / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / microbiology
  • Cell Differentiation / immunology
  • Cell Line
  • Chronic Periodontitis / immunology
  • Clonal Selection, Antigen-Mediated
  • Dendritic Cells / immunology
  • Forkhead Transcription Factors / analysis
  • GATA3 Transcription Factor / analysis
  • Humans
  • Immunologic Memory / immunology*
  • Isoenzymes / analysis
  • Isoenzymes / immunology
  • Macrophages / immunology
  • Mice
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / analysis
  • Osteoclasts / drug effects
  • Osteoclasts / immunology*
  • Porphyromonas gingivalis / classification
  • Porphyromonas gingivalis / immunology*
  • RANK Ligand / analysis
  • RANK Ligand / immunology*
  • Serogroup*
  • T-Box Domain Proteins / analysis
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / microbiology
  • T-bet Transcription Factor
  • Tartrate-Resistant Acid Phosphatase
  • Th1 Cells / immunology
  • Th17 Cells / immunology

Substances

  • Antigens, Bacterial
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • Isoenzymes
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RANK Ligand
  • RORC protein, human
  • T-Box Domain Proteins
  • T-bet Transcription Factor
  • TNFSF11 protein, human
  • Acid Phosphatase
  • Acp5 protein, mouse
  • Tartrate-Resistant Acid Phosphatase