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

Frontiers in Microbiology

Microbiology

Li Shi¹  Rong Bi¹  Hongwei Liao²  Jingyan Li²  Jingsi Yang²  Jiangli Liang²  Lukui Cai²  Guang Ji²  Yan Ma²  Yanling Yang³  Mingbo Sun³ 

[1] Laboratory of Immunogenetics, Institute of Medical Biology, Chinese Academy of Medical Science, Peking Union Medical College, Kunming, Yunnan, China;Laboratory of Vaccine Development, Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Kunming, China;The Affiliated Stomatology Hospital of Kunming Medical University, Center of Stomatology, Affiliated Hospital of Yunnan University, Kunming, Yunnan, China;

关键词: periodontal disease;    Porphyromonas gingivalis;    cGAS-STING signaling pathway;    proinflammatory cytokines;    RANKL;    osteoclast;    macrophage polarization;   

DOI  :  10.3389/fmicb.2023.1183415

 received in 2023-03-13, accepted in 2023-05-30,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

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Copyright © 2023 Bi, Yang, Liao, Ji, Ma, Cai, Li, Yang, Sun, Liang and Shi.