DEFECT IN KILLING OF INTRACELLULAR BACTERIA BY ACTIVATED MACROPHAGES
Some bacterial species (Mycobacteria, Listeria, Salmonella) are resistant to the killing mechanisms operating within phagocytic cells and therefore can survive and multiply within monocytes and macrophages. Effective immunity against these organisms depends on T-cell- (and NK-cell-) dependent macrophage activation. Studies in gene-disrupted mouse and human immunodeficiencies have identified that IL-12- and IL-23-dependent interferon gamma (IFN-γ) production is critically important for immunity against intracellular bacteral pathogens. This process is intitiated by the stimulation of Toll receptors on the surface of antigen-presenting cells by bacterial ligands such as mycobacterial lipoarabinomannan. This result in the secretion of IL-12 and IL-23 and TNF-α by the antigen-presenting cells. Binding of the IL-12 and IL-23 to their respective receptors, expressed on the surface of activated T cells and NK cells, induces these cells to secrete a further cytokine IFN-γ. IFN-γ acting in concert with TNF-α activates macrophages, which are then capable of killing intracellular pathogens (eg Mycobacteria and Salmonella).