Protective Responses in Tuberculosis: Induction of Genes for Interferon-gamma and Cytotoxicity by Mycobacterium tuberculosis and During Human Tuberculosis

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Abstract
The host effector mechanisms against Mycobacterium tuberculosis infection are not well understood, and this remains a problem in the development of new vaccines and immunotherapies in tuberculosis (TB). Here, we studied the expression of genes for interferon gamma (IFN-gamma) and molecules involved in lymphocyte-mediated cytotoxicity [granzyme B (grzB), perforin, granulysin and Fas ligand (FasL)] against M. tuberculosis-infected macrophages. The kinetics of expression of these molecules were first established in peripheral blood mononuclear cells (PBMC) of healthy donors, and then investigated in TB patients with and without HIV-1 coinfection and appropriate control groups. We found that only IFN-gamma and grzB were induced by M. tuberculosis in PBMC from healthy purified protein derivative skin test reactive subjects. However, expression of neither gene nor IFN-gamma protein correlated with intracellular M. tuberculosis growth containment by macrophages. Mycobacterium tuberculosis induction of IFN-gamma, but not grzB, mRNA expression was significantly lower (P < 0.03) in TB patients as compared with healthy subjects.