NOD-Like Receptor Activation by Outer Membrane Vesicles from Vibrio cholerae Non-O1 Non-O139 Strains Is Modulated by the Quorum-Sensing Regulator HapR
NOD-Like Receptor Activation by Outer Membrane Vesicles from Vibrio cholerae Non-O1 Non-O139 Strains Is Modulated by the Quorum-Sensing Regulator HapR
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DOI：
10.1128/iai.00754-10
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发表时间：
2011-04-01
影响因子：
3.1
通讯作者：
Kufer, T. A.
中科院分区：
文献类型：
--
作者：
Bielig, H.;Rompikuntal, P. K.;Kufer, T. A.
弧菌霍乱是水生系统的居民，也是人类严重脱水腹泻的病因之一。它也成为了不同种类的炎症反应的重要原因，尤其是非O1非O139非O139血清群（NOVC）的霍乱链球菌菌株与人类中这种感染有关。我们分析了源自NOVC菌株V：5/04的外膜外囊泡（OMV）的潜力，以诱导人类宿主细胞中的炎症反应。 V：5/04 OMV被人类上皮细胞和诱导的炎症反应所吸收。小型干扰RNA（siRNA）介导的基因敲低表明Novc OMV的炎症潜力部分由核苷酸结合结构域 - 富含亮氨酸的重复含有含有亮氨酸的重复含量的家庭成员NOD1介导。这些OMV含量的理化学分析以及HEK293T细胞中NOD1和NOD2报告基因测定，证实了OMV中NOD1和NOD2 Active Pepteptidoglycan的存在。此外，我们表明了群体感应调节剂HAPR的缺失，该调节剂模仿感染性生活方式，特别降低了V：5/04 OMV的炎症潜力及其激活NOD1和NOD2的能力。总之，我们的研究表明，NOVC OMV会在哺乳动物宿主细胞中介导的NOD1和NOD2介导的免疫反应。此外，我们提供的证据表明，群体感应机械在此过程中通过衰减在感染条件下OMV的炎症潜力在此过程中起着重要的调节作用。因此，这项工作确定了颤动如何影响宿主免疫反应的新方面，并在此过程中定义了群体感应机械的作用。
Vibrio cholerae is an inhabitant of aquatic systems and one of the causative agents of severe dehydrating diarrhea in humans. It has also emerged as an important cause of different kinds of inflammatory responses, and in particular, V. cholerae strains of the non-O1 non-O139 serogroups (NOVC) have been associated with such infections in human. We analyzed the potential of outer membrane vesicles (OMVs) derived from the NOVC strain V:5/04 to induce inflammatory responses in human host cells. V:5/04 OMVs were taken up by human epithelial cells and induced inflammatory responses. Small interfering RNA (siRNA)-mediated gene knockdown revealed that the inflammatory potential of NOVC OMVs was partially mediated by the nucleotide-binding domain-, leucine-rich repeat-containing family member NOD1. Physiochemical analysis of the content of these OMVs, in conjunction with NOD1 and NOD2 reporter assays in HEK293T cells, confirmed the presence of both NOD1 and NOD2 active peptidoglycan in the OMVs. Furthermore, we show that deletion of the quorum-sensing regulator HapR, which mimics an infective life style, specifically reduced the inflammatory potential of the V:5/04 OMVs and their ability to activate NOD1 and NOD2. In conclusion, our study shows that NOVC OMVs elicit immune responses mediated by NOD1 and NOD2 in mammalian host cells. Moreover, we provide evidence that the quorum-sensing machinery plays an important regulatory role in this process by attenuating the inflammatory potential of OMVs under infective conditions. This work thus identifies a new facet of how Vibrio affects host immune responses and defines a role for the quorum-sensing machinery in this process.