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Candida and host cell interactions associated with colonisation and infection

Rogers, Helen 2017. Candida and host cell interactions associated with colonisation and infection. PhD Thesis, Cardiff University.
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Abstract

Candida infections of humans are an increasingly prevalent problem. Most candidal infections are superficial, occurring on mucosal surfaces, however, systemic infection can arise in immunocompromised individuals and these are life threatening. Candida is recognised by host immune cells through pattern recognition receptors e.g. dectin-1. The immune cells then produce cytokines to drive adaptive immune responses. The type of T-helper (Th) cell response that occurs is an important factor in whether candidal colonisation or clearance occurs. The overall focus of this research was to employ in vivo and in vitro studies to assess the nature of the immune response to Candida albicans. Increased pro-inflammatory Th17 and Th1 responses were evident in denture stomatitis (DS) patients based on cytokine profiles. In chronic hyperplastic candidosis (CHC) tissues significantly higher levels of CD4+, IL-12A+, IL-17A+ and EBi3+ positive cells were detected by immunohistochemistry (IHC) compared to control tissues. This finding was indicative of an increased Th17 response in CHC. IHC detection of individual cytokine subunits in cells was more difficult to interpret, but suggested both IL-35 and IL-12 cytokines were present, indicating Treg and Th1 cell responses, respectively. Challenge of a human monocyte cell line and human peripheral blood mononuclear cells (PBMCs) with C. albicans resulted in IL-23 cytokine expression indicative of a Th17 response. Interestingly, lipopolysaccharide (LPS) was important in enhancing the ability of dendritic cells to recognise and phagocytose C. albicans via dectin-1. The recall response from PBMCs stimulated with C. albicans resulted in a significant Th17 recall response. Extrapolation of these findings to the host interaction with Candida requires additional clinical studies and assessment of other forms of superficial mucosal candidosis. This research does however indicate that host recognition of C. albicans leads to a predominantly pro-inflammatory Th17 response.

Item Type: Thesis (PhD)
Date Type: Submission
Status: Unpublished
Schools: Dentistry
Subjects: Q Science > Q Science (General)
R Medicine > RK Dentistry
Uncontrolled Keywords: candida albicans; host response; T helper cells
Date of First Compliant Deposit: 17 April 2018
Last Modified: 17 Apr 2018 08:37
URI: http://orca-mwe.cf.ac.uk/id/eprint/110724

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