Despite the rich oral microflora, infections within the oral cavity are rare. Rapid wound healing within the oral mucosa occurs, potentially due to the presence of oral mucosa lamina propria-progenitor cells (OMLP-PCs). OMLP-PCs are a novel population of multipotent cells known to possess immunosuppressive properties,through contact-independent mediated mechanisms. Many immunomodulatory soluble factors are also documented to have dual functions as antimicrobials; leading to the hypothesis that OMLP-PCs possess antibacterial properties in addition to their published immunoregulatory actions. The aim of this study was to investigate the antibacterial properties of OMLP-PCs and to define the mechanisms of action. A further aim of this study was to determine whether the antibacterial potential of OMLP-PCs was affected during disease, specifically Graft Versus Host Disease (GVHD). The antibacterial properties of OMLP-PCs were compared between cells isolated from healthy donors and patients with oral chronic GVHD. During this study it was determined that OMLP-PCs possess constitutive antibacterial properties against Gram positive and Gram negative bacteria which are mediated through the release of soluble factors. LL37 and Indoleamine 2,3-Dioxygenase are known to mediated the antibacterial properties of bone marrow-mesenchymal stem cells, however this study determined that these factors did not play a role in the OMLP-PCs antibacterial effects. It was established that osteoprotegerin, haptoglobin and prostaglandin E2 in part mediate the antibacterial effects of OMLP-PCs. For the first time, direct antibacterial properties of osteoprotegerin were demonstrated against Gram positive bacteria. Furthermore, OMLP-PCs isolated from GVHD patients did not display antibacterial properties. It was further established that the secretion of innate cell chemoattractants was dysregulated in OMLP-PCs isolated from GVHD patients compared to healthy controls. This finding demonstrates that during GVHD, the oral mucosa is unable to regulate the oral microflora and sufficiently recruit innate immune cells during infection.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:685535 |
| Date | January 2016 |
| Creators | Board Davies, Emma |
| Publisher | Cardiff University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://orca.cf.ac.uk/91227/ |
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