Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI 48109-1078, USA.
Mol Oral Microbiol. 2012 Dec;27(6):483-95. doi: 10.1111/omi.12001. Epub 2012 Sep 18.
Periodontitis is a polymicrobial oral infection characterized by the destruction of tooth-supporting structures that can be linked to systemic diseases such as cardiovascular disease, diabetes or rheumatoid arthritis. Porphyromonas gingivalis, a bacterium implicated in the etiology of periodontitis, has shown variation in inducing T-cell responses among different strains. Therefore, in this study we investigated the strain-specific immune response using a murine experimental model of periodontitis. Periodontitis was induced by P. gingivalis strains A7A1-28, W83 and W50, and later confirmed by the presence of P. gingivalis in the oral microflora and by alveolar bone resorption. Splenocytes were evaluated for gene expression, cellular proteins and cytokine expression. Dendritic cells were stimulated in vitro for T helper cell-cytokine profiling. Results showed that P. gingivalis had the ability to alter the systemic immune response after bacterial exposure. Strains W50 and W83 were shown to induce alveolar bone loss, whereas the A7A1-28 strain did not significantly promote bone resorption in mice. Splenocytes derived from mice infected with strains W50 and W83 induced expression of high levels of interleukin-4 (IL-4) but A7A1-28 stimulated increased IL-10. Stimulation of dendritic cells in vitro showed a similar pattern of cytokine expression of IL-12p40, IL-6 and transforming growth factor-β among strains. A distinct systemic response in vivo was observed among different strains of P. gingivalis, with IL-10 associated with the least amount of alveolar bone loss. Evaluation of pathogen-driven systemic immune responses associated with periodontal disease pathogenesis may assist in defining how periodontitis may impact other diseases.
牙周炎是一种多微生物口腔感染,其特征是破坏支持牙齿的结构,可能与心血管疾病、糖尿病或类风湿性关节炎等系统性疾病有关。牙龈卟啉单胞菌是牙周炎病因学中涉及的一种细菌,不同菌株在诱导 T 细胞反应方面表现出变异。因此,在这项研究中,我们使用牙周炎的小鼠实验模型研究了菌株特异性免疫反应。通过牙龈卟啉单胞菌菌株 A7A1-28、W83 和 W50 诱导牙周炎,随后通过口腔微生物群中存在牙龈卟啉单胞菌和牙槽骨吸收来确认。评估了脾细胞的基因表达、细胞蛋白和细胞因子表达。体外刺激树突状细胞以分析 T 辅助细胞细胞因子谱。结果表明,细菌暴露后,牙龈卟啉单胞菌具有改变全身免疫反应的能力。W50 和 W83 菌株显示出诱导牙槽骨丧失的能力,而 A7A1-28 菌株在小鼠中并未显著促进骨吸收。来自感染 W50 和 W83 菌株的小鼠的脾细胞诱导高水平白细胞介素-4 (IL-4) 的表达,但 A7A1-28 刺激增加白细胞介素-10 的表达。体外刺激树突状细胞显示出菌株之间细胞因子表达的类似模式,包括白细胞介素-12p40、白细胞介素-6 和转化生长因子-β。在体内观察到不同牙龈卟啉单胞菌菌株之间存在明显的全身反应,IL-10 与牙槽骨丧失量最少有关。评估与牙周病发病机制相关的病原体驱动的全身免疫反应可能有助于确定牙周炎如何影响其他疾病。