Outer Membrane Vesicles Prime and Activate Macrophage Inflammasomes and Cytokine Secretion In Vitro and In Vivo

Frontiers in Immunology

卷:8

Ashley Mansell¹  Jessica D. Cecil²  Alexis Perez-Gonzalez²  William Singleton²  Eric C. Reynolds²  Jason C. Lenzo²  James A. Holden²  Neil M. O’Brien-Simpson² 

[1] Department of Molecular and Translational Science, Monash University, Clayton, VIC, Australia;

[2] Oral Health CRC, Melbourne Dental School, Bio21 Institute, The University of Melbourne, Melbourne, VIC, Australia;

关键词: outer membrane vesicles;    macrophages;    inflammasomes;    Porphyromonas gingivalis;    Treponema denticola;    Tannerella forsythia;   

DOI  :  10.3389/fimmu.2017.01017

来源: DOAJ

【 摘 要 】

Outer membrane vesicles (OMVs) are proteoliposomes blebbed from the surface of Gram-negative bacteria. Chronic periodontitis is associated with an increase in subgingival plaque of Gram-negative bacteria, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia. In this study, we investigated the immune-modulatory effects of P. gingivalis, T. denticola, and T. forsythia OMVs on monocytes and differentiated macrophages. All of the bacterial OMVs were phagocytosed by monocytes, M(naïve) and M(IFNγ) macrophages in a dose-dependent manner. They also induced NF-κB activation and increased TNFα, IL-8, and IL-1β cytokine secretion. P. gingivalis OMVs were also found to induce anti-inflammatory IL-10 secretion. Although unprimed monocytes and macrophages were resistant to OMV-induced cell death, lipopolysaccharide or OMV priming resulted in a significantly reduced cell viability. P. gingivalis, T. denticola, and T. forsythia OMVs all activated inflammasome complexes, as monitored by IL-1β secretion and ASC speck formation. ASC was critical for OMV-induced inflammasome formation, while AIM2−/− and Caspase-1−/− cells had significantly reduced inflammasome formation and NLRP3−/− cells exhibited a slight reduction. OMVs were also found to provide both priming and activation of the inflammasome complex. High-resolution microscopy and flow cytometry showed that P. gingivalis OMVs primed and activated macrophage inflammasomes in vivo with 80% of macrophages exhibiting inflammasome complex formation. In conclusion, periodontal pathogen OMVs were found to have significant immunomodulatory effects upon monocytes and macrophages and should therefore influence pro-inflammatory host responses associated with disease.

【 授权许可】

Unknown