The effect of mycobacterial mycolic acids on the cytokine profile of the immune response in murine tuberculosis

Abstract

Mycobacterium tuberculosis (M. tuberculosis) , the etiological agent of tuberculosis, is an intracellular bacterium which persists within macrophages. Successful control of tuberculosis depends on T-cell-mediated immunity. Immune protection involves the development of a Th1 response characterised by the secretion of cytokines such as IL-12, IFN-γ and TNF-α. The progression towards disease in humans and mice is often associated with a Th2 response characterised by the secretion of cytokines such as I L-4 and I L-10. Mycolic acids, the major cell wall lipid of M. tuberculosis, were previously shown to have a marginally protective effect on the development of disease in Balb/c mice when administered intravenously at an optimal dose of 25 µg one week before intravenous M. tuberculosis infection. Here it is shown that the protective effect is highly significant when infection is done intranasally. The protective effect of 25 µg mycolic acids against tuberculosis could not be explained by induction of a longer lasting Th1 response in Balb/c mice. This was determined by using semi-quantitative RT-PCR on the mRNA of cytokines characteristic of the different immune responses. It was observed that maximum sensitivity was obtained at the lowest possible PCR cycle and template concentrations for the samples. Mycolic acids were the first non-protein antigens shown to induce an immune response after presentation on CD1 membrane proteins. Balb/c mice predominantly generate a Th1 response during the first 3 - 4 weeks of M. tuberculosis infection, whereas they generate a Th2 response in the following weeks. Even though the protective effect of 25 µg mycolic acids could not be associated with a prolonged Th1 immune response in infected mice, it did induce IL-12 and IL-10 mRNA in uninfected mice. These cytokines are primarily.