Thesis Type: Doctorate
Institution Of The Thesis: Orta Doğu Teknik Üniversitesi, Faculty of Arts and Sciences, Department of Biology, Turkey
Approval Date: 2018
Student: ESİN ALPDÜNDAR BULUT
Consultant: MAYDA GÜRSELAbstract:
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.