M.Sc. / The induction of heat shock proteins (HSPs) in human monocytes during a pathogen challenge is a sophisticated selective response and plays an important role in cytoprotection from inflammation-related stress, including oxidative injury. We investigated the accumulation of the inducible isoform of the 70 kDa HSP, Hsp70, in peripheral blood monocytes from 12 healthy donors in response to Mycobacterium tuberculosis (M.tb) using flow cytometry, biometabolic labeling or Western blot analysis. Cells from each donor, prepared on two different occasions, were exposed to virulent (H37Rv) and attenuated (H37Ra) strains of M.tb at two bacterium : monocyte ratios (1:1 and 10:1) for 3 h and allowed to recover for an additional 2 h or 24 h. In spite of a prominent inter-individual variation, H37Ra (1:1, 2 h) significantly induced the mean Hsp70 accumulation (p<0.05) compared to normal cells, while H37Rv (10:1, 24 h) significantly suppressed the mean Hsp70 levels (p<0.001) in monocyte compared to normal monocytes or monocytes exposed to H37Ra. Survival of H37Rv-infected monocytes showed a significant correlation with Hsp70 levels. These results suggest a protective role of Hsp70 in host defense against mycobacterial infection. Cell death due to insufficient endogenous levels of Hsp70 implies a novel pathogenic strategy for virulence of M. tuberculosis.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:uj/uj:3236 |
| Date | 27 August 2012 |
| Creators | Mafoko, Baatseba |
| Source Sets | South African National ETD Portal |
| Detected Language | English |
| Type | Thesis |
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