The study of the human microbiota is of enormous importance because it represents a significant diverse microbial population that co-habits the intestine and influences host physiology, immune homeostasis, gene and protein expression and, importantly, overall health status. The microbiota is crucial in regulation of immune tolerance. Epithelial cells are considered an important cell population involved in host microbial interactions as they are the first intact cell layer in contact with bacteria colonizing the gut. Understanding how bacteria influence the host response in health and in disease may improve the understanding of how inflammation and inflammatory bowel diseases (IBD) develop and also provide insights into which bacterial population promote health and maintain immune homeostasis. The main objective of this thesis was to investigate the response of epithelial cells to commensal and pathogenic bacteria and metagenomic clones (derived from the human gut microbiota). Both commensal and pathogenic bacteria present microbial-associated molecular patterns (MAMPs) that are recognised by innate immune receptors such as Toll-like receptors (TLRs). The mechanisms by which commensal bacteria maintain immune tolerance in the gut, whereas pathogens induce strong immune responses, are not fully understood. We investigated the hypothesis that commensal bacteria control immune homeostasis, in part, by regulating NF-κB mediated signalling. In particular, the effect of specific gut microbes on the expression of the NF-κB repressor A20, a zinc protein that is encoded by TNFAIP3 gene, which induces strong down-regulation of the canonical NF-kB pathway was investigated. This thesis revealed that immune regulation by both pathogenic and commensal bacteria involves both positive and negative regulation of the NF-kB pathway mediated by specific MAMPs and metabolites. The significance of these findings in relation to immune homeostasis and inflammation are discussed
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:577626 |
| Date | January 2013 |
| Creators | Ferraria, Vanessa |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=201655 |
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