Department of Oral Biology, University of Florida, Gainesville, FL 32610, United States.
Department of Periodontology, University of Michigan, Ann Arbor, MI 48109, United States.
Arch Oral Biol. 2018 Mar;87:125-130. doi: 10.1016/j.archoralbio.2017.12.016. Epub 2017 Dec 16.
Periodontal diseases are a class of non-resolving inflammatory diseases, initiated by a pathogenic subgingival biofilm, in a susceptible host, which if left untreated can result in soft and hard tissue destruction. Oral epithelial cells are the first line of defense against microbial infection within the oral cavity, whereby they can sense the environment through innate immune receptors including toll-like receptors (TLRs). Therefore, oral epithelial cells directly and indirectly contribute to mucosal homeostasis and inflammation, and disruption of this homeostasis or over-activation of innate immunity can result in initiation and/or exacerbation of localized inflammation as observed in periodontal diseases. Dynamics of TLR signaling outcomes are attributable to several factors including the cell type on which it engaged. Indeed, our previously published data indicates that oral epithelial cells respond in a unique manner when compared to canonical immune cells stimulated in a similar fashion. Thus, the objective of this study was to evaluate the role of oral epithelial cell innate sensing on periodontal disease, using a murine poly-microbial model in an epithelial cell specific knockout of the key TLR-signaling molecule MyD88 (B6). Following knockdown of MyD88 in the oral epithelium, mice were infected with Porphorymonas gingivalis and Aggregatibacter actinomycetemcomitans by oral lavage 4 times per week, every other week for 6 weeks. Loss of oral epithelial cell MyD88 expression resulted in exacerbated bone loss, soft tissue morphological changes, soft tissue infiltration, and soft tissue inflammation following polymicrobial oral infection. Most interestingly while less robust, loss of oral epithelial cell MyD88 also resulted in mild but statistically significant soft tissue inflammation and bone loss even in the absence of a polymicrobial infection. Together these data demonstrate that oral epithelial cell MyD88-dependent TLR signaling regulates the immunological balance within the oral cavity under conditions of health and disease.
牙周病是一类由致病的龈下生物膜在易感宿主中引发的非自限性炎症性疾病，如果不治疗，可能会导致软硬组织破坏。口腔上皮细胞是口腔内抵御微生物感染的第一道防线，通过先天免疫受体（包括 Toll 样受体（TLR））感知环境。因此，口腔上皮细胞直接和间接地促进黏膜的稳态和炎症，而这种稳态的破坏或先天免疫的过度激活可导致局部炎症的发生和/或加剧，如牙周病中观察到的那样。TLR 信号转导结果的动态归因于几个因素，包括与其相互作用的细胞类型。事实上，我们之前发表的数据表明，与以类似方式刺激的经典免疫细胞相比，口腔上皮细胞以独特的方式做出反应。因此，本研究的目的是使用一种上皮细胞特异性 TLR 信号分子 MyD88（B6）缺失的多微生物小鼠模型，评估口腔上皮细胞先天感知在牙周病中的作用。在口腔上皮细胞中敲低 MyD88 后，每周通过口腔灌洗 4 次，每隔一周感染牙龈卟啉单胞菌和伴放线放线杆菌，共 6 周。口腔上皮细胞 MyD88 表达缺失导致多微生物口腔感染后骨丢失、软组织形态学变化、软组织浸润和软组织炎症加重。最有趣的是，尽管不那么明显，但即使在没有多微生物感染的情况下，口腔上皮细胞 MyD88 缺失也会导致轻度但具有统计学意义的软组织炎症和骨丢失。这些数据共同表明，口腔上皮细胞 MyD88 依赖性 TLR 信号调节口腔内健康和疾病状态下的免疫平衡。
