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Title: Characterisation of bacterial profiles in chronic rhinosinusitis
Author: Hayes, Stephen M. A.
ISNI:       0000 0004 8501 8057
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2018
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Chronic rhinosinusitis (CRS) with or without nasal polyps (NP) affects up to 15% of the UK population significantly affecting quality of life and impacting heavily on health care resources. Despite millions of pounds spent on research each year, the underlying cause of CRS remains unknown. Bacteria have been implicated in playing a role in mediating the ongoing inflammation in CRS. Bacteria possess the ability to quickly adapt to environmental changes, readily interchanging between planktonic, biofilm and intracellular profiles. Emerging evidence suggests that CRS is the result of a locally dysregulated innate immune system caused by changes in bacterial profiles in a bid for survival. The work presented in this thesis aimed to clarify this proposed theory through characterisation of bacterial profiles in CRS and analysis of the effect on the local innate immune system at a cellular level. A prospective study was performed using ex-vivo sinonasal mucosal and NP tissue from CRS patients, and sinonasal mucosa from non-CRS patients undergoing transsphenoidal pituitary surgery as a control. Tissue was analysed using the LIVE/DEAD® BacLight™ viability kit, fluorescent in situ hybridisation, scanning electron microscopy, transmission electron microscopy, confocal laser scanning microscopy and immunohistochemistry. An explant tissue model was developed to explore histological changes at the host-environment interface after addition of exogenous Staphylococcus aureus (S aureus) and Staphylococcus enterotoxin B (SEB). An in vitro cell culture model was developed to investigate cellular changes resulting from mast cell-S aureus interactions. Surface-related biofilms were identified on CRS sinonasal mucosa. S aureus was the commonest microbe identified. Sodium nitroprusside appeared to have little or no effect on dispersal of surface-related CRS biofilms. In NP, bacteria were sub-epithelial and within mast cells (intracellular). This is the first reported study to observe intracellular S aureus within mast cells in NP. The presence of SEB significantly increased the internalisation of S aureus into mast cells. S aureus entered mast cells through phagocytosis and via extracellular traps. Proliferating intracellular S aureus led to mast cell expansion and eventual rupture, seeding viable S aureus and proinflammatory mediators into the extracellular space. These findings demonstrate the ability of S aureus in CRS to manipulate the host's innate immune system in order to facilitate survival. Adaptation of bacteria into different profiles results in different pathophysiological effects. The intermittent dispersal of active planktonic bacteria from surface-related bacterial biofilms on nonpolypoidal mucosa mediates the ongoing chronic inflammation and symptom relapse in CRS. Intracellular S aureus within mast cells could act as a reservoir for bacteria constantly seeding into the extracellular environment leading to the build-up of proinflammatory cytokines and mediators, thus promoting tissue oedema and potentially nasal polyp growth. These findings suggest that NP formation may be an indirect consequence of a S aureus survival strategy to evade host defences.
Supervisor: Pender, Sylvia ; Salib, Rami Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available