MyD88-mediated innate sensing by oral epithelial cells controls periodontal inflammation
MyD88-mediated innate sensing by oral epithelial cells controls periodontal inflammation
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DOI：
10.1016/j.archoralbio.2017.12.016
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发表时间：
2018-03-01
影响因子：
3
通讯作者：
Wallet, Shannon M.
中科院分区：
文献类型：
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作者：
Delitto, Andrea E.;Rocha, Fernanda;Wallet, Shannon M.
牙周病是一类非消退性炎症性疾病，由易感宿主中的致病性龈下生物膜引发，如果不进行治疗，可导致软组织和硬组织破坏。口腔上皮细胞是抵抗口腔内微生物感染的第一道防线，由此它们可以通过先天免疫受体（包括Toll样受体（TLR））来感知环境。因此，口腔上皮细胞直接和间接地促进粘膜稳态和炎症，这种稳态的破坏或先天免疫的过度激活可能会导致局部炎症的启动和/或加剧，正如在牙周病中观察到的那样。TLR信号传导结果的动力学可归因于几个因素，包括其参与的细胞类型。事实上，我们先前发表的数据表明，与以类似方式刺激的典型免疫细胞相比，口腔上皮细胞以独特的方式应答。因此，本研究的目的是评估口腔上皮细胞先天感知对牙周病的作用，使用上皮细胞特异性敲除关键TLR信号分子MyD 88（B6（K5Cre.MyD88plox））的鼠多微生物模型。在口腔上皮中敲除MyD 88后，通过每周4次、每隔一周的口腔灌洗用牙龈卟啉单胞菌和伴放线菌聚集杆菌感染小鼠，持续6周。口腔上皮细胞MyD 88表达的缺失导致多种微生物口腔感染后骨丢失加重、软组织形态学改变、软组织浸润和软组织炎症。最有趣的是，虽然不太稳健，但口腔上皮细胞MyD 88的损失也导致轻度但统计学显著的软组织炎症和骨丢失，即使在没有多种微生物感染的情况下。这些数据共同表明，口腔上皮细胞MyD 88依赖性TLR信号传导调节健康和疾病条件下口腔内的免疫平衡。
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(K5Cre.MyD88plox)). Following knockdown of MyD88 in the oral epithelium, mice were infected with Porphoryntonas 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 poly microbial 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.