Abstract
M.Sc. (Biochemistry)
Mycobacterium tuberculosis (M.tb) infection remains a persistent cause of illness and fatality across the world, however this infectious disease (Tuberculosis or TB) is particularly problematic in Sub-Saharan Africa. Compounding the issue is the fact that many individuals have weakened immune systems due to the Human Immunodeficiency Virus (HIV) as well as malnutrition. This dissertation presents an investigation into; a) basal plasma 25(OH)D3 levels to determine if this form of vitamin D, commonly quantified as a marker of vitamin D status, could potentially have an influence on the subsequent innate immune response to M.tb, b) the innate immune response in healthy Black and White as well as male and female South African blood donors when the isolated monocyte-derived macrophages are stimulated by the synthetic mycobacterial peptide, Pam3CSK4 (TLR2/1 elicitor), thereby mimicking M.tb infection, c) the effect of in vitro monocyte-derived macrophage 1,25(OH)2D3 supplementation and the functional influence of the Vitamin D Receptor (VDR)-mediated immune pathway on antimicrobial peptide and autophagosome formation and d) although not investigated directly, our findings may have implications on whether Vitamin D supplementation could be used as adjunct treatment and as a preventative measure to reduce the spread of TB, especially strains that are Extensively Drug Resistant TB (XDR-TB) or Multi-Drug Resistant TB (MDR-TB). Ensuring vitamin D sufficiency may be an important benefit for the immune systems of individuals who are particularly susceptible to M.tb. The research was performed under the supervision of Professor Liza Bornman from the Department of Biochemistry at the Faculty of Science, University of Johannesburg.