AUTHOR=Bi Rong , Yang Yanling , Liao Hongwei , Ji Guang , Ma Yan , Cai Lukui , Li Jingyan , Yang Jingsi , Sun Mingbo , Liang Jiangli , Shi Li 

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

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1183415

DOI=10.3389/fmicb.2023.1183415

ISSN=1664-302X

ABSTRACT=<p>Periodontitis is an inflammatory disease initiated by periodontopathogenic bacteria in the dental plaque biofilms. Understanding the role of <italic>Porphyromonas gingivalis</italic> (<italic>P. gingivalis</italic>), a keystone pathogen associated with chronic periodontitis, in the inflammatory response is crucial. Herein, we investigated whether <italic>P. gingivalis</italic> 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 <italic>in vitro</italic> and in a mouse model. Additionally, in an experimental model of periodontitis using <italic>P. gingivalis</italic>, Sting<sup>Gt</sup> 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 <italic>P. gingivalis</italic>. 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 <italic>P. gingivalis</italic>-induced inflammatory response that leads to chronic periodontitis.</p>