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Title: The skin immune response to Malassezia furfur
Author: Gallagher, Helen P.
ISNI:       0000 0001 3486 9263
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2001
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The paradoxical nature of M furfur colonisation versus infection in dermatological disease is subject to much research. The aim of this experimental work was to measure the innate immune response of the skin to M. furfur, via the use of skin models. Living skin equivalents (LSE), excised breast reduction tissue (BRT) and keratinocyte (KC) monolayers were all utilised in an attempt to elucidate the possible immune evasive and stimulatory capabilities of M. furfur. The constitutive production of human p defensin 2 (HBD-2), an inducible antimicrobial peptide, was measured KC monolayers, LSEs and BRT. In addition the skin model's response to fungal challenge was elucidated. Wide variation in the basal expression of HBD-2 was detected in all skin model donors. M. furfur cell wall and killed whole M. furfur initiated a slight depression in HBD-2 expression by KC monolayers, however these results were not statistically significant in all donors and merely indicated a trend. Likewise KC monolayers, BRT and LSEs reacted to viable M. furfur with slight inhibition of HBD-2 production at 24hr with subsequent stimulation of expression. However donor variation in this pattern was detected and these results were not continuously significant. Due to the non-continuous nature of these measurements these results were inconclusive. As M furfur infection of the skin is associated with alteration of the normal pigmentation in patients, melanin synthesis by B16 mouse melanoma cells and BRT was assessed in response to M. furfur. Viable M. jurjur and C. albicans stimulated an increase in melanin synthesis in B16 mouse melanoma cells. The ability of viable M. furfur cells to stimulate melanin synthesis appeared to be localised within the cytoplasm of the organism. However, this 'viable cell stimulation' did not appear to be restricted to M. furfur, as C. albicans also stimulated melanin synthesis. On BRT there was little difference in the melanin and tyrosinase production of BRT in reponse to M. furfur and C. albicans growth. The capacity of M. furfur and C. albicans cell wall to alter the cytokine profile of KCs was also measured and KC monolayers exhibited a time-dependent increase in IL-la, IL-8 and ET-1 expression in response to M. furfur and C. albicans cell wall. C. albicans cell wall initiated a significantly greater increase in the expression of these cytokines by the KCs. However little correlation between the mRNA production and peptide production was measured using RT-PCR. Growth of M furfur and C. albicans on the skin models was assessed using scanning electron microscopy (SEM) and histological observation of the colonized tissue. Growth was also compared by means of viable cell counts. The effect of growth on the proliferation of the epidermis was measured by counting the number of proliferating cells in the basal layer of the epidermis of each tissue. Growth of M. furfur and C. albicans was detected on LSE and BRT and hyphal transformation of both organisms was observed on BRT and LSE, although hyphal transformation of C. albicans was found more commonly on the LSE. Indeed, overall growth of C. albicans was more widespread and rapid on LSE than it was on BRT. By contrast M. furfur appeared to undergo hyphal transformation more frequently on BRT, and this feature was donor-dependent. The viability of M. furfur varied when tested on BRT from different donors or on different batches of LSE. The proliferative index of the tissues indicated that growth of both M. furfur and C. albicans initiated an increase in the proliferation of the BRT and LSE epidermis. Overall, these studies show that growth of M. furfur and C. albicans differs in the various skin models and this effect was dependent on the different qualities of the donor tissue and donor KCs. The growth of M. furfur, while slower than that of C. albicans, does stimulate a larger increase in the proliferation of the BRT epidermis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral