Department of Oral Biology, School of Dental Medicine, University at Buffalo, State University of New York, Buffalo, New York, USA.
Mucosal Immunol. 2013 Mar;6(2):415-26. doi: 10.1038/mi.2012.85. Epub 2012 Sep 12.
Tannerella forsythia is a pathogen implicated in periodontitis, an inflammatory disease of the tooth-supporting tissues often leading to tooth loss. This key periodontal pathogen is decorated with a unique glycan core O-glycosidically linked to the bacterium's proteinaceous surface (S)-layer lattice and other glycoproteins. Herein, we show that the terminal motif of this glycan core acts to modulate dendritic cell effector functions to suppress T-helper (Th)17 responses. In contrast to the wild-type bacterial strain, infection with a mutant strain lacking the complete S-layer glycan core induced robust Th17 and reduced periodontal bone loss in mice. Our findings demonstrate that surface glycosylation of this pathogen may act to ensure its persistence in the host likely through suppression of Th17 responses. In addition, our data suggest that the bacterium then induces the Toll-like receptor 2-Th2 inflammatory axis that has previously been shown to cause bone destruction. Our study provides a biological basis for pathogenesis and opens opportunities in exploiting bacterial glycans as therapeutic targets against periodontitis and a range of other infectious diseases.
福赛斯拟杆菌是一种与牙周炎相关的病原体，牙周炎是一种牙齿支持组织的炎症性疾病，常导致牙齿脱落。这种关键的牙周病原体表面有一层独特的聚糖核心，通过 O-糖苷键与细菌的蛋白质表面（S）层晶格和其他糖蛋白连接。本文中，我们发现该聚糖核心的末端基序可调节树突状细胞的效应功能，抑制辅助性 T 细胞 17（Th17）反应。与野生型细菌株不同，感染缺失完整 S 层聚糖核心的突变株可诱导强烈的 Th17 反应，并减少小鼠牙周骨丢失。我们的研究结果表明，这种病原体表面的糖基化可能通过抑制 Th17 反应来确保其在宿主体内的持续存在。此外，我们的数据表明，细菌随后诱导 Toll 样受体 2-Th2 炎症轴，先前的研究表明该炎症轴会导致骨破坏。我们的研究为发病机制提供了生物学基础，并为利用细菌糖作为治疗牙周炎和一系列其他传染病的靶点提供了机会。
