Effect of Porphyromonas gingivalis outer membrane vesicles on gingipain-mediated detachment of cultured oral epithelial cells and immune responses
Effect of Porphyromonas gingivalis outer membrane vesicles on gingipain-mediated detachment of cultured oral epithelial cells and immune responses
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DOI：
10.1016/j.micinf.2013.10.005
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发表时间：
2014-01-01
影响因子：
5.8
通讯作者：
Senpuku, Hidenobu
中科院分区：
文献类型：
--
作者：
Nakao, Ryoma;Takashiba, Shogo;Senpuku, Hidenobu
牙龈卟啉单胞菌（Porphyromonas gingivalis）是牙周病的主要病原菌，其外膜囊泡（OMV）含有脂多糖（LPS）和牙龈卟啉蛋白酶（gingipains）等毒力因子。在这项研究中，我们研究了牙龈卟啉单胞菌感染期间OMV在宿主免疫反应和组织破坏中的潜在作用。首先，我们发现牙周炎患者的血清对OMV产生的野生型菌株的反应性明显强于同基因OMV缺失菌株。发现OMV具有高度抗原性，因为OMV吸收患者血清大大降低了与牙龈卟啉单胞菌全细胞的反应性。OMV的LC-MS/MS分析揭示了多种形式的牙龈卟啉菌蛋白酶和几种牙龈卟啉菌蛋白酶相关蛋白。使用患者血清的OMV的蛋白质印迹揭示了类似于由牙龈卟啉菌蛋白酶抗血清识别的OMV抗原的保守的免疫反应性抗原谱，这表明OMV相关的牙龈卟啉菌蛋白酶在触发抗体介导的对牙龈卟啉菌感染的免疫应答中的潜在作用。当OMV被添加到口腔鳞状上皮细胞系的单层中时，OMV引起细胞脱离，这通过用抗牙龈菌蛋白酶抗血清预孵育OMV来抑制。这些数据表明，牙龈卟啉菌蛋白酶负载OMV可能有助于牙周病的组织破坏作为一种载体的抗原和活性蛋白酶。(C)2013年巴斯德研究所。由Elsevier Masson SAS出版。All rights reserved.
Porphyromonas gingivalis is a major etiological agent of periodontal diseases and the outer membrane vesicles (OMVs) contain virulence factors such as LPS and gingipains. In this study, we investigated the potential role of the OMVs in host immune response and tissue destruction during P. gingivalis infection. Firstly, we found that sera from periodontitis patients had significantly stronger reactivity against an OMV-producing wild type strain than the isogenic OMV-depleted strain. OMVs were found to be highly antigenic, as absorption of patient sera with OMVs greatly reduced reactivity with whole cells of P. gingivalis. LC-MS/MS analysis of OMVs revealed multiple forms of gingipains and several gingipain-related proteins. Western blots of OMVs using patient sera revealed a conserved immunoreactive antigen profile resembling the profile of OMV antigens that were recognized by gingipain antiserum, suggesting a potential role of OMV-associated gingipains in triggering antibody-mediated immune responses to P. gingivalis infection. When OMVs were added to a monolayer of an oral squamous epithelial cell line, OMVs caused cell detachment, which was inhibited by preincubating OMVs with anti-gingipain antiserum. These data suggest that gingipain-laden OMVs may contribute to tissue destruction in periodontal diseases by serving as a vehicle for the antigens and active proteases. (C) 2013 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.