Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.724909
Title: Investigating the role of hepcidin and iron homeostasis in mycobacterial infection
Author: Kandt, Rachel
ISNI:       0000 0004 6421 4681
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2015
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Abstract:
Tuberculosis, caused by Mycobacterium tuberculosis (M.tb) is one of the world's most prevalent infectious diseases. The quest for an effective vaccine and an immune correlate of protection are on going. Previous literature reports links between the iron status of the host and disease severity, but the underlying mechanisms are not clear. Here, a murine model of M.tb infection was used to determine the effect of M.tb infection on the expression of hepcidin and other genes involved in the regulation of iron homeostasis. Female BALB/c and C57BL/6 mice were infected with M.tb Erdman via aerosol. Change in expression of iron-responsive genes was measured by liver qRT- PCR. Bacterial burden was determined in organ homogenates. The effect of iron deficiency on disease outcome was also investigated, where mice fed an iron-deficient or control diet were infected with M.tb. To determine whether hepcidin has a role in disease outcome, Hamp1-/- mice were also infected with M.tb. In the time course experiments, changes in hepcidin kinetics post-M.tb infection were observed, which were likely regulated by BMP/SMAD and not IL-6/JAK-STAT signalling. In the iron- restricted diet experiments, iron deficiency did not reproducibly affect bacterial burden. Moreover, deletion of Hamp1 did not affect outcome of in vivo M.tb infection. The data in this thesis indicate that iron homeostasis is altered during M.tb infection, but that altering host iron homeostasis by inducing iron deficiency or deleting the hepcidin gene does not compromise the host's ability to control infection.
Supervisor: McShane, Helen Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.724909  DOI: Not available
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