Helicobacter pylori Outer Membrane Vesicle Size Determines Their Mechanisms of Host Cell Entry and Protein Content

Frontiers in Immunology

Lorinda Turner¹  Kimberley D’Costa¹  Georg Ramm²  Richard L. Ferrero³  Andrew F. Hill⁵  Mitch Shambrook⁵  Camden Lo⁷  David L. Steer⁸  Maria Kaparakis-Liaskos⁹  Natalie J. Bitto⁹ 

[1] Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Melbourne, VIC, Australia;Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC, Australia;Department of Microbiology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC, Australia;Department of Physiology, Anatomy and Microbiology, School of Life Sciences, La Trobe University, Melbourne, VIC, Australia;La Trobe Institute for Molecular Sciences, La Trobe University, Melbourne, VIC, Australia;Monash Biomedical Proteomics Facility, Monash University, Clayton, VIC, Australia;Monash Micro Imaging, Monash University, Clayton, VIC, Australia;Monash University, Clayton, VIC, Australia;Research Centre for Extracellular Vesicles, School of Molecular Sciences, La Trobe University, Melbourne, VIC, Australia;

关键词: bacterial membrane vesicles;    endocytosis;    macropinocytosis;    pathogenesis;    proteomics;    outer membrane vesicles;   

DOI  :  10.3389/fimmu.2018.01466

来源: DOAJ

【 摘 要 】

Gram-negative pathogens ubiquitously shed outer membrane vesicles (OMVs) that play a central role in initiating and regulating pathogenesis in the host. Due to their highly inflammatory nature, OMVs are extensively being examined for their role in mediating disease in addition to their applications in innovative vaccines. A key mechanism whereby OMVs mediate inflammation and disease progression is dependent on their ability to enter host cells. Currently, the role of OMV size on determining their mechanism of cellular entry and their protein composition remains unknown. In this study, we examined the mechanisms whereby OMV size regulates their mode of entry into epithelial cells, in addition to their protein cargo and composition. We identified that a heterogeneous sized population of Helicobacter pylori OMVs entered epithelial cells via macropinocytosis, clathrin, and caveolin-dependent endocytosis. However, smaller OMVs ranging from 20 to 100 nm in size preferentially entered host cells via caveolin-mediated endocytosis. Whereas larger OMVs ranging between 90 and 450 nm in size entered host epithelial cells via macropinocytosis and endocytosis. Most importantly, we identified the previously unknown contribution that OMV size has on determining their protein content, as fewer and less diverse bacterial proteins were contained within small OMVs compared to larger OMVs. Collectively, these findings identify the importance of OMV size in determining the mechanisms of OMV entry into host cells, in addition to regulating their protein cargo, composition, and subsequent immunogenicity. These findings have significant implications in broadening our understanding of the bacterial regulation of virulence determinants and immunogenic proteins associated with OMVs, their role in mediating pathogenesis and in refining the design and development of OMV-based vaccines.

【 授权许可】

Unknown