Figure 3: PPAR-mediating suppression of parasiticidal response in leishmaniasis. The sandfly vector carries leishmanial promastigotes to the mammalian host. The parasites then transform into amastigotes within phagolysosomes of host macrophages. Type 1 immunity, with T helper 1 (Th1) releasing interferon γ (IFNγ), leads to classically activated macrophages (caMac). CaMac produce nitric oxide from inducible nitric oxide synthase (iNOS), interleukin-1 (IL-1), tumor necrosis factor (TNF), and reactive oxygen and nitrogen intermediates (ROI, RNI) that act to eliminate the amastigotes. Type 2 immunity, with Th2 releasing IL-4, leads to activation of peroxisome proliferator-activated receptor (PPAR) and alternatively activated macrophages (aaMac). AaMac produce arginase, IL-10, transforming growth factor β (TGFβ), and PPAR that allow amastigote propagation. PPAR agonists (GW7845 and GW0742) and some phytochemicals (curcumin) can activate PPAR and promote aaMac maturation. Activation of PPAR allows parasite survival as a chronic parasitic infection.