Thesis

Modelling the immune response to Leishmania mexicana in mice

Creator
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Awarding institution
  • University of Strathclyde
Date of award
  • 2014
Thesis identifier
  • T13746
Qualification Level
Qualification Name
Department, School or Faculty
Abstract
  • Leishmania is a protozoan parasite endemic in 88 countries worldwide with over 12 million people currently infected and 2 million new infections annually. The visceral version of the disease can be fatal if left untreated, and the severe cutaneous/mucocutaneous lesions caused by the other types can have severe socio-economic repercussions. The first line of defence against these parasites is the innate branch of the immune system and although in some cases these cells are able to resolve the infection, in many cases the disease persists due to the parasites abilities to manipulate the immune system and render these cells ineffective. This project aimed to model the murine response to L.mexicana, examining the kinetics of recruitment and uptake, the migration of neutrophils, DCs and macrophages and the phenotypes of these cells after contact with parasites using flow cytometry, in vivo imaging, confocal microscopy and ELISA. We found that neutrophils are the most numerous cells recruited to the site of infection and persisted the longest. DCs rapidly take up L.mexicana promastigotes in vitro within minutes though the most significant increase occurs within the first half hour and uptake plateauxed by 60 minutes. Fixing the parasites with paraformaldehyde did not affect promastigote uptake by DCs but it did affect uptake by neutrophils, suggesting that L.mexicana facilitates its own uptake by neutrophils but not by DCs. This has not been shown before but supports existing literature. Infected cells did not seem to migrate into the lymphatic system, and showed deficiencies in expression of activation markers and production of IL-12. Together these results illustrate the abilities of L.mexicana to manipulate the immune system to cause persistent infection and give a glimpse into the early recruitment and uptake events of innate cells in response to the parasite.
Resource Type
DOI
Date Created
  • 2014
Former identifier
  • 1032703

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