Microbiome-mediated incapacitation of interferon lambda production in the oral mucosa

Carlos J. Rodriguez-Hernandez, Kevin J. Sokoloski, Kendall S. Stocke, Himabindu Dukka, Shunying Jin, Melissa A. Metzler, Konstantin Zaitsev, Boris Shpak, Daonan Shen, Daniel P. Miller, Maxim N. Artyomov, Richard J. Lamont, Juhi Bagaitkar

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Here, we show that Porphyromonas gingivalis (Pg), an endogenous oral pathogen, dampens all aspects of interferon (IFN) signaling in a manner that is strikingly similar to IFN suppression employed by multiple viral pathogens. Pg suppressed IFN production by down-regulating several IFN regulatory factors (IRFs 1, 3, 7, and 9), proteolytically degrading STAT1 and suppressing the nuclear translocation of the ISGF3 complex, resulting in profound and systemic repression of multiple interferon-stimulated genes. Pg-induced IFN paralysis was not limited to murine models but was also observed in the oral tissues of human periodontal disease patients, where overabundance of Pg correlated with suppressed IFN generation. Mechanistically, multiple virulence factors and secreted proteases produced by Pg transcriptionally suppressed IFN promoters and also cleaved IFN receptors, making cells refractory to exogenous IFN and inducing a state of broad IFN paralysis. Thus, our data show a bacterial pathogen with equivalence to viruses in the down-regulation of host IFN signaling.

Original languageEnglish
Article numbere2105170118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number51
DOIs
StatePublished - Dec 21 2021

Keywords

  • Interferon lambda
  • Oral epithelial cells
  • Periodontitis
  • Porphyromonas gingivalis
  • Viral infection

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