NOD-Like Receptor Activation by Outer Membrane Vesicles from Vibrio cholerae Non-O1 Non-O139 Strains Is Modulated by the Quorum-Sensing Regulator HapR

被引:63
作者
Bielig, H. [1 ]
Rompikuntal, P. K. [2 ,3 ]
Dongre, M. [2 ,3 ]
Zurek, B. [1 ]
Lindmark, B. [2 ,3 ]
Ramstedt, M. [4 ]
Wai, S. N. [2 ,3 ]
Kufer, T. A. [1 ]
机构
[1] Univ Cologne, Inst Med Microbiol Immunol & Hyg, D-50931 Cologne, Germany
[2] Umea Univ, Dept Mol Biol, S-90187 Umea, Sweden
[3] Umea Univ, Umea Ctr Microbial Res, S-90187 Umea, Sweden
[4] Umea Univ, Dept Chem, S-90187 Umea, Sweden
基金
瑞典研究理事会;
关键词
CONSTITUTIVELY ACTIVE VARIANT; NF-KAPPA-B; BACTERIAL PEPTIDOGLYCAN; ESCHERICHIA-COLI; EPITHELIAL-CELLS; HOST RECOGNITION; IMMUNITY; RELEASE; VIRULENCE; CYTOTOXIN;
D O I
10.1128/IAI.00754-10
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:1418 / 1427
页数:10
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