Porphyromonas gingivalis Promotes Unrestrained Type I Interferon Production by Dysregulating TAM Signaling via MYD88 Degradation

Gabriel Mizraji, Maria Nassar, Hadas Segev, Hafiz Sharawi, Luba Eli-Berchoer, Tal Capucha, Tsipora Nir, Yaara Tabib, Avraham Maimon, Shira Dishon, Lior Shapira, Gabriel Nussbaum, Asaf Wilensky*, Avi Hai Hovav

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Whereas type I interferons (IFNs-I) were proposed to be elevated in human periodontitis, their role in the disease remains elusive. Using a bacterial-induced model of murine periodontitis, we revealed a prolonged elevation in IFN-I expression. This was due to the downregulation of TAM signaling, a major negative regulator of IFN-I. Further examination revealed that the expression of certain TAM components was reduced as a result of prolonged degradation of MYD88 by the infection. As a result of such prolonged IFN-I production, innate immunological functions of the gingiva were disrupted, and CD4+ T cells were constitutively primed by dendritic cells, leading to elevated RANKL expression and, subsequently, alveolar bone loss (ABL). Blocking IFN-I signaling restored proper immunological function and prevented ABL. Importantly, a loss of negative regulation on IFN-I expression by TAM signaling was also evident in periodontitis patients. These findings thus suggest a role for IFN-I in the pathogenesis of periodontitis.

Original languageAmerican English
Pages (from-to)419-431
Number of pages13
JournalCell Reports
Volume18
Issue number2
DOIs
StatePublished - 10 Jan 2017

Bibliographical note

Publisher Copyright:
© 2017 The Authors

Keywords

  • GAS6
  • Porphyromonas gingivalis, MYD88
  • interferon
  • mucosal immunity
  • oral mucosa
  • periodontitis

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