Down-modulation of cytokine- and TLR4-mediated DC activation and IL-12 production in DCs by Leishmania amastigotes. L. amazonensis amastigotes can efficiently enter mDCs, preventing and actively suppressing DC maturation/activation and IL-12 production. Alterations in amastigote-infected, LPS/IFN-stimulated DCs are mostly attributed to suppressed activation and/or accelerated degradation of components in the JAK/STAT, NF-κB, and IFN regulator factor (IRF) pathways via parasite-derived proteinases and oligopeptidases rather than to the endogenous production of IL-10. Alterations in DC activation and function can result in an impaired activation of NK cells and parasite-specific Th1 cells, leading to uncontrolled parasite replication and persistent infection.