Genetics of susceptibility to tuberculosis.
Convincing evidence that activated macrophages play a critical role in control of
mycobacterial diseases has been clearly established from animal and in-vitro studies.
Macrophages produce a variety of molecules upon appropriate stimulation, which act in
concert towards eventual killing of bacteria. People with SUb-optimal macrophage
activation are more susceptible to infection with intracellular pathogens. My project
aims to answer two questions relating to genetic regulation of macrophage activation in
tuberculosis: do macrophage genes regulate microbial-induced responses and do
macrophage genes influence susceptibility to tuberculosis? A whole blood assay was
used to investigate IFN-y responsiveness in healthy individuals and those who develop
tuberculosis in The Gambia. Cytokine responses to lipopolysaccaride (LPS),
Lipoarabinomanan (LAM) and the enhancing effect of IFN-y on these stimulants were
measured. LPS induced IL-l 0 levels was higher in recovered TB cases than in controls
(p=0.02). LPS and LAM induced cytokines were highly correlated (p<0.0001)
similarly, levels of IL-IB and TNF were highly correlated (P