Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.659840
Title: Plasticity of macrophages from helminth infection
Author: Mylonas, Katharine Jude Louise
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2008
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Abstract:
A murine model for filarial infection has been used as an in vivo source of nematode-elicited Macrophages (NeMs). Mice are surgically implanted into the peritoneal cavity with adult Brugia malayi. By one week post-infection, the PEC population is dominated by macrophages that display IL-4 dependent features such as the expression of Arginase1, RELM-α and Ym1. In light of the increasing evidence that macrophages show functional adaptivity, it was decided to study the NeMs response to pro-inflammatory Th1 activating signals as a model to investigate whether the switch between alternative and classical activation can occur in macrophages differentiated in an in vivo infection setting. Despite the long-term exposure to Th2 cytokines and anti-inflammatory signals in vivo, we found that NeMs were not terminally differentiated but could switch from alternative activation to a more classically activated phenotype in response to LPS/IFN-γ. This was reflected by a switch in the enzymatic pathway for arginine metabolism from arginase to iNOS and the reduced expression of RELM-α and Ym1. To ask whether these Ms could be induced to be antimicrobial, we also carried out infections with “type 1”-inducing pathogens. It was found that LPS/IFN-γ treated NeMs were able to control infection with Leishmania mexicana as effectively as LPS/IFN-γ activated thioglycollate-elicited macrophages (ThioMs) and parasite killing was mediated by nitric oxide production. NeMs were also infected with Mycobacterium bovis BCG. It was found that NeMs responded to low doses of BCG by controlling it for the entire timeframe of the study, i.e. 6 days. NeMs responded to high doses of BCG infection with early control of infection and high levels of apoptosis, and that this phenotype is independent of IL-4.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.659840  DOI: Not available
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