Macrophage inducible C-type lectin (Mincle) recognizes glycosylated surface (S)-layer of the periodontal pathogen Tannerella forsythia.
Macrophage inducible C-type lectin (Mincle) recognizes glycosylated surface (S)-layer of the periodontal pathogen Tannerella forsythia.
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DOI：
10.1371/journal.pone.0173394
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Sharma A
中科院分区：
文献类型：
--
作者：
Chinthamani S;Settem RP;Honma K;Kay JG;Sharma A
口腔病原体连翘Tannerella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撑组织的破坏，经常导致牙齿脱落。连翘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，使细菌能够表达一个糖基化的表面(S)层，该层由两个高分子量的糖蛋白修饰而成。连翘s层与抗原呈递细胞（如巨噬细胞）的细胞因子反应的调节有关，巨噬细胞在与牙周炎相关的炎症中起着重要作用。巨噬细胞诱导的c型凝集素受体（Mincle）是一种fcr γ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。在这项研究中，我们旨在确定Mincle是否可能参与了连翘s层的识别和巨噬细胞对细菌的细胞因子反应的调节。利用重组Mincle- fc融合蛋白的结合研究表明，Mincle与连翘s层具有特异性的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，在连连花及其s层刺激的巨噬细胞中，Mincle/ s层相互作用在诱导促炎性和抗炎性细胞因子分泌中的作用。综上所述，这些研究表明Mincle是一个重要的巨噬细胞受体，参与巨噬细胞对连翘的细胞因子反应的调节，因此可能在协调宿主对连翘的免疫反应中发挥关键作用。
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.