Commensal bacteria-derived membrane vesicles supress Th-1 dominated immune responses in vaccinated and tumor-bearing mice
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1
Middle East Technical University, Department of Biological Sciences, Türkiye
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2
Bilkent University, Molecular Biology and Genetics, Türkiye
Constitutive secretion of extracellular membrane vesicles is a common feature of cells from all domains of life including Archaea, Bacteria, and Eukarya. Although the contribution of gram negative bacterial outer membrane vesicles in disease pathogenesis has been extensively studied, whether commensal bacteria constitutively secrete such vesicles is still unknown. Given the importance of microbiota as regulators of immune homeostasis, we aimed to assess the immunomodulatory properties of extracellular vesicles secreted by 3 different human commensal lactobacilli isolates in comparison to E.coli derived outer membrane vesicles. AFM microscopy, dynamic light scattering and zeta potential measurements revealed that commensal-derived membrane vesicles (MVs) were nearly 250 nm in diameter and had high negative charge densities (-40 mV). Mice immunized with an inactivated viral vaccine against the foot an mouth disease virus showed suppressed FMD-specific IgG2a response when the vaccine contained MVs derived from commensals but not from E.coli. Similarly, commensal MVs suppressed anti-OVA antibody responses in OVA immunized mice and exacerbated tumor progression following challenge with EG.7 tumor cells, suggesting that commensal-derived MVs ameliorate Th-1 dominated inflammatory responses. In contrast, encapsulation of cyclic-di-GMP in commensal-derived MVs enhanced the immunostimulatory properties of this cyclic di-nucleotide and reversed the tolerogenic potential of the MVs. These results indicate that human commensal bacteria-derived membrane vesicles can have powerful immunomodulatory effects and can have potential therapeutic applications as novel anti-inflammatory agents.
Acknowledgements
EA is supported by Ministry of Science, Industry and Technology, Turkey within the scope of SANTEZ project (1414.STZ.2012-1).
Keywords:
membrane vesicles,
commensal bacteria,
adjuvant,
Vaccination,
gram positive bacteria
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Innate immunity
Citation:
Alpdundar
E,
Yildiz
S,
Bayyurt
B,
Ozcan
M,
Gucluler
G,
Bayik
D,
Gungor
B,
Gursel
İ and
Gursel
M
(2013). Commensal bacteria-derived membrane vesicles supress Th-1 dominated immune responses in vaccinated and tumor-bearing mice.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00101
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Received:
11 Mar 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Mrs. Esin Alpdundar, Middle East Technical University, Department of Biological Sciences, Ankara, 06800, Türkiye, esinalpdundar@gmail.com