Peroxisome Proliferator-Activated Receptor-γ-Mediated Polarization of Macrophages in Leishmania Infection
Scheme of Leishmania interaction with mediators of the resolution process during inflammation. When infected sandflies bite, promastigotes enter the neutrophils and macrophages that are recruited to the inflamed site of injection. The parasite can, by itself, activate the infected host cells to produce PPAR activators. This includes PPARγ agonists such as the bioactive lipids 15d-PGJ2 and LXA4 from the arachidonic acid pathways. Engulfment of apoptotic neutrophils and IL-4 from T helper 2 cells can activate PPARγ as well. Activation of PPARγ polarizes the host macrophage towards the alternatively activated macrophage (M2) phenotype, which would produce arginase to divert substrate from iNOS and thus reduce the production of nitric oxide. As such, the parasite can survive and multiply within the host’s macrophages, and the infection becomes chronic.
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