Immunomodulatory effects of commensal bacteria-derived membrane vesicles


Thesis Type: Postgraduate

Institution Of The Thesis: Orta Doğu Teknik Üniversitesi, Faculty of Arts and Sciences, Department of Biology, Turkey

Approval Date: 2013

Student: ESİN ALPDÜNDAR

Consultant: MAYDA GÜRSEL

Abstract:

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 from 5 different human commensal bacteria isolates in comparison to E.coli derived outer membrane vesicles (MVs). AFM microscopy, dynamic light scattering and zeta potential measurements revealed that commensal-derived membrane vesicles (MVs) were 50- 300 nm in diameter and had high negative charge densities (-40 mV). Mouse spleen cells stimulated with commensal derived MVs secreted lower levels of pro-inflammatory cytokines (IFN and TNF) and higher levels of IL-10 when compared to E.coli derived MVs. Similarly, commensal derived MVs failed to stimulate the maturation of antigen presenting cells. Mice immunized with an inactivated viral vaccine against the foot and mouth disease virus showed suppressed FMD-specific IgG2a response when the vaccine contained MVs derived from commensals but not from E.coli. 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.