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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
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Microbiome-mediated incapacitation of interferon lambda production in the oral mucosa

Carlos J Rodriguez-Hernandez1,2, Kevin J Sokoloski2, Kendall S Stocke1

  • 1Department of Oral Immunology and Infectious Diseases, School of Dentistry, University of Louisville, Louisville, KY 40202.

Proceedings of the National Academy of Sciences of the United States of America
|December 18, 2021
PubMed

Insights

Porphyromonas gingivalis, an oral pathogen, suppresses host interferon (IFN) signaling similarly to viruses. This bacterial pathogen causes systemic IFN paralysis by interfering with key signaling pathways, impacting the immune response.

Area of Science:

  • Immunology
  • Microbiology
  • Oral Biology

Background:

  • Porphyromonas gingivalis (Pg) is an oral bacterium linked to periodontal disease.
  • Interferon (IFN) signaling is crucial for antiviral defense and immune regulation.
  • Viral pathogens are known to suppress IFN signaling.

Purpose of the Study:

  • To investigate the effect of Porphyromonas gingivalis on host interferon signaling.
  • To elucidate the mechanisms by which Pg interferes with IFN responses.
  • To determine if Pg-induced IFN suppression is observed in human periodontal disease.

Main Methods:

  • Analysis of IFN regulatory factors (IRFs) and STAT1 degradation in response to Pg.
  • Assessment of ISGF3 complex nuclear translocation.
  • Evaluation of IFN-stimulated gene expression.
  • Examination of oral tissues from human periodontal disease patients.

Main Results:

  • Pg significantly suppressed IFN production and signaling pathways.
  • Pg down-regulated IRFs, degraded STAT1, and inhibited ISGF3 complex translocation.
  • Pg-induced IFN suppression was observed in human periodontal tissues, correlating with Pg abundance.
  • Pg virulence factors and proteases were found to suppress IFN promoters and cleave IFN receptors.

Conclusions:

  • Porphyromonas gingivalis actively suppresses host interferon signaling, mimicking viral strategies.
  • This bacterial pathogen induces a state of systemic IFN paralysis, compromising host immunity.
  • Pg's ability to disrupt IFN pathways is a significant factor in its pathogenicity and association with periodontal disease.
Keywords:
Interferon lambdaPorphyromonas gingivalisoral epithelial cellsperiodontitisviral infection

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