Growth Factor and Th2 Cytokine Signaling Pathways Converge at STAT6 to Promote Arginase Expression in Progressive Experimental Visceral Leishmaniasis

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Visceral leishmaniasis (VL), caused by the intracellular protozoan Leishmania donovani, is a progressive infection that is particularly common in impoverished populations of the world. People die from this disease unless it is treated. We used an experimental infection model that mimics the clinical and pathological features of human VL to study how the parasite causes this severe disease. We found that host macrophages infected with Leishmania donovani are activated in a way that leads to the expression of arginase, an enzyme that counteracts the cell's mechanisms that control the infection. This disease-promoting activation pathway was driven by the convergence of growth factor and cytokine signaling pathways and activation of the transcription factor STAT6. Chemical inhibition of signaling through the fibroblast growth factor receptor-1 (FGFR-1) or insulin-like growth factor-1 receptor (IGF-IR), or genetic knockdown of STAT6 led to reduced expression of arginase and enhanced control of the infection by macrophages. This indicates that the growth factor signaling pathways together with the cytokine pathways promote this disease. Interventions designed to disrupt this signaling could help in the treatment of VL.

Vyšlo v časopise: Growth Factor and Th2 Cytokine Signaling Pathways Converge at STAT6 to Promote Arginase Expression in Progressive Experimental Visceral Leishmaniasis. PLoS Pathog 10(6): e32767. doi:10.1371/journal.ppat.1004165
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004165

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