Figure 7.

Schematic model for the role of IL-12 in type 1 cytokine cascades in both T cells and macrophages during intracellular infection. Upon interaction with intracellular pathogens such as mycobacteria, macrophages release IL-12 and TNF-α. The release of TNF-α is IL-12–independent. The essential role of IL-12 in host responses rests, in part, on its potent effect on IFN-γ production from different cell types. On one hand, it stimulates Th1 differentiation and IFN-γ production from CD4⁺ Th1 cells. This IFN-γ activates macrophages via a paracrine mechanism. On the other hand, IL-12, together with intracellular pathogens, stimulates IFN-γ release from macrophages. This IFN-γ may activate macrophages via a potent autocrine mechanism. Two macrophage activation pathways through IFN-γ are indicated with broken lines.