Chinthamani Sreedevi, Settem Rajendra P, Honma Kiyonobu, Kay Jason G, Sharma Ashu
Dept. of Oral Biology, University at Buffalo, Buffalo, New York, United States of America.
PLoS One. 2017 Mar 6;12(3):e0173394. doi: 10.1371/journal.pone.0173394. eCollection 2017.
The oral pathogen Tannerella forsythia is implicated in the development of periodontitis, a common inflammatory disease that leads to the destruction of the gum and tooth supporting tissues, often leading to tooth loss. T. forsythia is a unique Gram-negative organism endowed with an elaborate protein O-glycosylation system that allows the bacterium to express a glycosylated surface (S)-layer comprising two high molecular weight glycoproteins modified with O-linked oligosaccharides. The T. forsythia S-layer has been implicated in the modulation of cytokine responses of antigen presenting cells, such as macrophages, that play a significant role during inflammation associated with periodontitis. The macrophage-inducible C-type lectin receptor (Mincle) is an FcRγ-coupled pathogen recognition receptor that recognizes a wide variety of sugar containing ligands from fungal and bacterial pathogens. In this study, we aimed to determine if Mincle might be involved in the recognition of T. forsythia S-layer and modulation of cytokine response of macrophages against the bacterium. Binding studies using recombinant Mincle-Fc fusion protein indicated a specific Ca2+-dependent binding of Mincle to T. forsythia S-layer. Subsequent experiments with Mincle-expressing and Mincle-knockdown macrophages revealed a role for Mincle/S-layer interaction in the induction of both pro- and anti-inflammatory cytokine secretion in macrophages stimulated with T. forsythia as well as its S-layer. Together, these studies revealed Mincle as an important macrophage receptor involved in the modulation of cytokine responses of macrophages against T. forsythia, and thus may play a critical role in orchestrating the host immune response against the bacterium.
口腔病原体福赛斯坦纳菌与牙周炎的发展有关，牙周炎是一种常见的炎症性疾病，会导致牙龈和牙齿支持组织的破坏，常常导致牙齿脱落。福赛斯坦纳菌是一种独特的革兰氏阴性菌，具有复杂的蛋白质O-糖基化系统，该系统使该细菌能够表达一种糖基化的表面（S）层，该层由两种经O-连接寡糖修饰的高分子量糖蛋白组成。福赛斯坦纳菌的S层与抗原呈递细胞（如巨噬细胞）的细胞因子反应调节有关，巨噬细胞在与牙周炎相关的炎症过程中起重要作用。巨噬细胞诱导型C型凝集素受体（Mincle）是一种与FcRγ偶联的病原体识别受体，可识别来自真菌和细菌病原体的多种含糖配体。在本研究中，我们旨在确定Mincle是否可能参与福赛斯坦纳菌S层的识别以及巨噬细胞针对该细菌的细胞因子反应的调节。使用重组Mincle-Fc融合蛋白的结合研究表明，Mincle与福赛斯坦纳菌S层存在特异性的Ca2+依赖性结合。随后对表达Mincle和敲低Mincle的巨噬细胞进行的实验表明，Mincle/S层相互作用在福赛斯坦纳菌及其S层刺激的巨噬细胞中促炎和抗炎细胞因子分泌的诱导中发挥作用。总之，这些研究表明Mincle是一种重要的巨噬细胞受体，参与调节巨噬细胞针对福赛斯坦纳菌的细胞因子反应，因此可能在协调宿主针对该细菌的免疫反应中起关键作用。
