Suppression of T-cell chemokines by Porphyromonas gingivalis

Infect Immun. 2013 Jul;81(7):2288-95. doi: 10.1128/IAI.00264-13. Epub 2013 Apr 15.

Abstract

Porphyromonas gingivalis is a major pathogen in periodontal disease and is associated with immune dysbiosis. In this study, we found that P. gingivalis did not induce the expression of the T-cell chemokine IP-10 (CXCL10) from neutrophils, peripheral blood mononuclear cells (PBMCs), or gingival epithelial cells. Furthermore, P. gingivalis suppressed gamma interferon (IFN-γ)-stimulated release of IP-10, ITAC (CXCL11), and Mig (CXCL9) from epithelial cells and inhibited IP-10 secretion in a mixed infection with the otherwise stimulatory Fusobacterium nucleatum. Inhibition of chemokine expression occurred at the level of gene transcription and was associated with downregulation of interferon regulatory factor 1 (IRF-1) and decreased levels of Stat1. Ectopic expression of IRF-1 in epithelial cells relieved P. gingivalis-induced inhibition of IP-10 release. Direct contact between P. gingivalis and epithelial cells was not required for IP-10 inhibition. These results highlight the immune-disruptive potential of P. gingivalis. Suppression of IP-10 and other Th1-biasing chemokines by P. gingivalis may perturb the balance of protective and destructive immunity in the periodontal tissues and facilitate the pathogenicity of oral microbial communities.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Bacteroidaceae Infections / immunology
  • Bacteroidaceae Infections / microbiology
  • Cells, Cultured
  • Chemokine CXCL10 / genetics
  • Chemokine CXCL10 / immunology*
  • Chemokine CXCL11 / genetics
  • Chemokine CXCL11 / immunology
  • Chemokine CXCL9 / immunology
  • Epithelial Cells / immunology*
  • Epithelial Cells / microbiology
  • Fusobacterium Infections / immunology
  • Fusobacterium Infections / microbiology
  • Fusobacterium nucleatum / immunology
  • Gingiva / cytology
  • Humans
  • Interferon Regulatory Factor-1 / genetics
  • Interferon Regulatory Factor-1 / immunology
  • Interferon-gamma / immunology
  • Porphyromonas gingivalis / immunology*
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / microbiology*
  • Transcription, Genetic

Substances

  • CXCL10 protein, human
  • CXCL11 protein, human
  • CXCL9 protein, human
  • Chemokine CXCL10
  • Chemokine CXCL11
  • Chemokine CXCL9
  • IRF1 protein, human
  • Interferon Regulatory Factor-1
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Interferon-gamma