Porphyromonas gingivalis induces an inflammatory response via the cGAS-STING signaling pathway in a periodontitis mouse model

Abstract

Periodontitis is an inflammatory disease initiated by periodontopathogenic bacteria in the dental plaque biofilms. Understanding the role of Porphyromonas gingivalis (P. gingivalis), a keystone pathogen associated with chronic periodontitis, in the inflammatory response is crucial. Herein, we investigated whether P. gingivalis infection triggers the expression of the type I IFN gene and various cytokines and leads to activation of the cGAMP synthase–stimulator of IFN genes (cGAS-STING) pathway both in vitro and in a mouse model. Additionally, in an experimental model of periodontitis using P. gingivalis, StingGt mice showed lower levels of inflammatory cytokines and bone resorption than wild-type mice. Furthermore, we report that a STING inhibitor (SN-011) significantly decreased inflammatory cytokine production and osteoclast formation in a periodontitis mouse model with P. gingivalis. In addition, STING agonist (SR-717) -treated periodontitis mice displayed enhanced macrophage infiltration and M1 macrophage polarization in periodontal lesions compared with that in vehicle-treated periodontitis mice. In conclusion, our results demonstrate that the cGAS-STING signaling pathway may be one of the key mechanisms crucial for the P. gingivalis-induced inflammatory response that leads to chronic periodontitis.

Methylome-wide analysis in systemic microbial-induced experimental periodontal disease in mice with different susceptibility

“…Intriguingly, Franchin M et al.’s (2023) ( Franchin et al., 2023 ) study on periodontal disease variations in Balb/c, C57bl/6, and C57bl/10 mice uncovered compelling correlations. Their findings unveiled reduced bone resorption and diminished pro-inflammatory cytokine levels in C57bl/6-10 mice compared to Balb/c mice, accompanied by heightened activation of the PI3K/Akt pathway and attenuated activation of the mTOR pathway in a ligature-induced periodontitis model ( Laplante and Sabatini, 2012 ; Bi et al., 2023 ). Corroborating these outcomes, our study employing a gavage model also demonstrated diminished bone resorption in C57bl/6 mice relative to Balb/c mice.…”