Immune modulatory effects of pediococcus pentosaceus derived membrane vesicles: mechanism of action and therapeutic applications

Alpdündar Bulut, Esin
In our previous studies, we characterized 5 different human gram positive commensal bacteria derived membrane vesicles (MVs) and compared their activity with non-pathogenic E.coli derived membrane vesicles. Results showed that commensal bacteria derived MVs had immunomodulatory properties whereas non-pathogenic E.coli derived membrane vesicles had immune stimulatory properties. In this thesis, we aimed to focus our attention to Pediococcus pentosaceus-derived MVs that displayed the highest immunomodulatory activity. In an immunization model, Pediococcus pentosaceus-derived MVs supressed anti-OVA specific IgG1 and IgG2c and CTL responses. Analysis of MV effect on different cell types showed that MVs exerted an immunomodulatory response by generating M2 macrophages and myeloid derived suppressor cells (MDSCs) but not regulatory T cells. MVs’ anti-inflammatory effects were also tested in acute inflammation models established in mice. In zymosan induced peritonitis model, MVs ameliorated excessive inflammation by reducing neutrophil recruitment to peritoneal cavity and inhibiting macrophage loss caused by inflammation. In dextran sodium sulphate (DSS) induced acute colitis model, post-treatment with MVs (Day 0 and 3) prevented colon shortening and loss of crypt architecture. In an excisional wound healing model, intraperitoneal MV administration accelerated wound closure through recruitement of PD-L1 expressing myeloid cells to the wound site. Collectively, these results indicate that Pediococcus pentosaceus derived membrane vesicles activates suppressor – regulatory cell types and can be used as potent anti-inflammatory agents for the treatment of inflammatory or autoimmune diseases.


Immunomodulatory effects of commensal bacteria-derived membrane vesicles
Alpdündar, Esin; Gürsel, Mayda; Department of Biology (2013)
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 vesic...
DynaDom: structure-based prediction of T cell receptor inter-domain and T cell receptor-peptide-MHC (class I) association angles
Hoffmann, Thomas; Marıon, Antoıne; Antes, Iris (Springer Science and Business Media LLC, 2017-02-02)
Background: T cell receptor (TCR) molecules are involved in the adaptive immune response as they distinguish between self- and foreign-peptides, presented in major histocompatibility complex molecules (pMHC). Former studies showed that the association angles of the TCR variable domains (Va/V beta) can differ significantly and change upon binding to the pMHC complex. These changes can be described as a rotation of the domains around a general Center of Rotation, characterized by the interaction of two highly...
Differential activation of immune cells by commensal versus pathogen-derived bacterial RNA
Özcan, Mine; Gürsel, Mayda; Department of Biology (2014)
Immunological mechanisms contributing to distinguishing signals derived from commensal versus pathogenic bacteria is an active area of research and recent evidence suggests that commensal and pathogens may express different variants of pathogen associated molecular patterns (PAMP). In this thesis, we propose that as a major member of PAMP, bacterial RNAs derived from commensal and pathogens may have distinct immunostimulatory activities due to differentially recognition by the host immune system. In order t...
Tamoxifen Increases Membrane Fluidity at High Concentrations
Severcan, Feride; Kazanci, Nadide; Zorlu, Faruk (Portland Press Ltd., 2000-6-1)
There are contradictory results in the literature relating to the effect of tamoxifen on membrane fluidity. The present work investigates the effect of tamoxifen on membrane dynamics to find out whether the concentration of tamoxifen can be one of the factors in this discrepancy. Turbidity (absorbance at 440 nm) and Fourier transform infrared spectroscopic studies reveal that tamoxifen causes opposite effects on membrane fluidity at low (1 mol.%) and high (30 mol.%) tamoxifen concentrations. Low tamoxifen c...
Chromosome segregation in Escherichia coli division: A free energy-driven string model
Fan, J.; Tuncay, Kağan; Ortoleva, P. J. (Elsevier BV, 2007-08-01)
Although the mechanisms of eukaryotic chromosome segregation and cell division have been elucidated to a certain extent, those for bacteria remain largely unknown. Here we present a computational string model for simulating the dynamics of Escherichia coli chromosome segregation. A novel thermal-average force field accounting for stretching, bending, volume exclusion, friction and random fluctuation is introduced. A Langevin equation is used to simulate the chromosome structural changes. The mechanism of ch...
Citation Formats
E. Alpdündar Bulut, “Immune modulatory effects of pediococcus pentosaceus derived membrane vesicles: mechanism of action and therapeutic applications,” Ph.D. - Doctoral Program, Middle East Technical University, 2018.