The PPARG signaling pathway in human macrophages in response to virulent M

Model of the PPARγ signaling pathway in human macrophages in response to virulent M. tuberculosis or ManLAM. Shown is a schematic based on our results along with those in the literature of how virulent M. tuberculosis infection or ManLAM stimulation induces PPARγ-mediated immunosuppression in macrophages. M. tuberculosis or ManLAM binds to the MR, which leads to upregulation of PPARγ expression through an MR-dependent signaling pathway and, simultaneously, to activation of MAPK-p38-mediated cPLA2, which leads to the release and hydrolysis of AA from the plasma membrane to generate the ligand for PPARγ (15-d-PGJ2). Activated PPARγ heterodimerizes with RXR, and they bind to PPREs in the IL-8 and COX2 promoters, thereby inducing their expression as well as expression of the MR. Activation of PPARγ leads to transrepression of NF-κB activity but promotes the generation of Th2 cytokines through PGE2 production.

Publication

Mycobacterium tuberculosis Activates Human Macrophage Peroxisome Proliferator-Activated Receptor γ Linking Mannose Receptor Recognition to Regulation of Immune Responses. () Murugesan V. S. Rajaram, et al. J Immunol. ;185(2):929-942. Figure: F11. All organisms Homo sapiens Drosophila melanogaster

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