Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.634172
Title: The homeostasis and function of plasmatocytes in adult Drosophila
Author: Woodcock, Katie
Awarding Body: King's College London (University of London)
Current Institution: King's College London (University of London)
Date of Award: 2013
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Abstract:
Many key immune pathway genes in vertebrates have conserved Drosophila counterparts; therefore, the fly has become an influential model for the study of innate immunity. The Drosophila immune response consists of a humoral response; characterised by the production of anti-microbial peptides and cytokines and a cellular response; mediated by plasmatocytes, the fly analogue cell to the mammalian macrophage. Plasmatocytes have been studied in detail during the embryonic and larval stages of development however, plasmatocyte homeostasis and function in adult flies remains poorly understood. This thesis firstly characterises plasmatocytes in adult Drosophila in terms of their numbers, expression markers and proliferative potential. Secondly the plasmatocyte response to dietary lipids is studied in adult flies, as a model for the mammalian macrophage response to dietary lipids. Excessive dietary fat consumption in humans is associated with an increased incidence of high fat diet related diseases, including type II diabetes and atherosclerosis. Numerous aspects of high fat diet induced disease pathology in mammals are attributed to lipid induced inflammation, in which macrophage mediated lipid scavenging and/or sensing is believed to be of central importance. We found that as dietary fat content increased; flies exhibited a rise in triglyceride and glucose levels, whilst simultaneously up regulating expression of the IL-6-like JAK-STAT cytokine unpaired3 (upd3), in addition, plasmatocytes adopted a lipid laden foam cell-like morphology. These phenotypes are similar to those observed in humans during high fat diet induced diseases. Interestingly plasmatocyte depletion or plasmatocyte specific knock down of the CD36-like scavenger receptor croquemort (crq) or cytokine upd3 in flies was sufficient to rescue various high fat diet induced phenotypes. Findings in this thesis identify a plasmatocyte specific and therefore macrophage specific role in the progression of high fat diet disease pathophysiology, which could prove significant in allowing for a better understanding of high fat diet disease aetiology in mammals.
Supervisor: Geissmann, Frederic Henri Lucien ; Dionne, Marc Stuart ; Taams, Leonie Suzanne Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.634172  DOI: Not available
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