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Streptococcus mutans outer membrane vesicles affect inflammasome activation and the glycolysis of macrophages

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机构: [1]Second Hosp Shijiazhuang, Shijiazhuang 050000, Peoples R China [2]Handan Stomatol Hosp, Handan 056000, Peoples R China [3]Cangzhou Peoples Hosp, Cangzhou 061000, Peoples R China [4]Gucheng Cty Hosp Hebei Provence, Gucheng 253800, Peoples R China [5]Hebei Med Univ, Dept Stomatol, Hosp 4, Shijiazhuang 050000, Peoples R China
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关键词: Oral bacteria S mutans OMVs Macrophages Inflammasome Glycolysis Biofilm

摘要:
Recent studies indicate that bacterial outer membrane vesicles (OMVs) play a significant role in bacterial virulence and pathogenicity. Streptococcus mutans (S. mutans), a principal pathogen in dental caries, secretes a substantial number of OMVs. However, the impact of S. mutans OMVs on oral health and their underlying pathogenic mechanisms remain poorly understood. Macrophages were the initial innate immune cells to respond to bacterial invaders and their products. Therefore, we purified S. mutans OMVs, which stimulated macrophages. Compared to controls, RT-PCR and ELISA analyses revealed that S. mutans OMVs significantly increased the production of IL-1 beta, IL-6, TNF-alpha and IL-8, with IL-1 beta being notably elevated. IL-1 beta production and secretion are tightly regulated by the inflammasome. Western blot analyses demonstrated that S. mutans OMVs upregulated the expression of inflammasome components, including NLRP3, NLRC4, ASC and AIM2, with a marked increase in NLRP3 expression. Silencing different inflammasome components with siRNA revealed a reduction in IL-1 beta secretion induced by S. mutans OMVs, particularly through NLRP3. Additionally, ATP production and K+ efflux were found to be crucial for NLRP3 activation. Prolonged stimulation with S. mutans OMVs resulted in increased lactate production and elevated expression of glycolysis-related genes Glut-1, PFKFB3, and HK I, indicating that S. mutans OMVs significantly induce macrophage glycolysis. Furthermore, S. mutans OMVs were shown to enhance biofilm formation, increase S. mutans colonisation on epithelial cells, and inhibit macrophage phagocytosis, thereby improving the survival of S. mutans in the oral cavity. In summary, S. mutans OMVs promote the survival of S. mutans in the mouth through multiple mechanisms, potentially influencing the development of dental caries.

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大类 | 3 区 医学
小类 | 3 区 免疫学 3 区 微生物学
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大类 | 3 区 医学
小类 | 3 区 免疫学 3 区 微生物学
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Q2 MICROBIOLOGY Q3 IMMUNOLOGY

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第一作者机构: [1]Second Hosp Shijiazhuang, Shijiazhuang 050000, Peoples R China
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