Figure 9

The effects of IL-12 and IL-27 on human macrophages during mycobacterial infection. (A) Infected macrophages express p28 and EBI3 resulting in secretion of IL-27. IL-27 downregulates the expression of V-ATPase and negatively regulates other mediators of the phagosomal/lysosomal pathway, such as CD63 and cathepsin D. (B) Modulation of the cytokine environment by supplying IL-12 and neutralizing IL-27 enhances the expression of CD63 and V-ATPase resulting in acidification of phagosomes that harbor mycobacteria. CD63 and V-ATPase may be recruited to the phagosome directly. Alternatively, CD63 and V-ATPase may first be recruited to the lysosomes that subsequently fuse with phagosomes. The enhancement of acidification requires IFN-γ and promotes processing of cathepsin D to the mature form.