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. 2014 Jun 26;10(6):e1004165. doi: 10.1371/journal.ppat.1004165

Figure 10. Working model for convergent signaling of growth factors and cytokines in the induction of arg1 in VL.

Figure 10

L. donovani infection induces the production of IL-4, IL-10 and FGF-2 in the spleen. FGFR is activated, as is IGF-IR by a yet to be identified host or parasite ligand. JAK kinases are phosphorylated through the activated cytokine or growth factor receptors, which lead to IRS-1/2, AKT, ERK, and STAT activation. Translocated STAT6, and possibly STAT3 lead to the transcriptional activation of arginase, which generates polyamines from arginine and leads to parasite growth. These transcription factors also contribute to the polarization macrophages toward an M2 phenotype, which is more permissive to L. donovani survival and growth. The collective effect of AKT, ERK, and STAT3 activation, and the generation of polyamines, are likely to lead to growth, proliferation and survival of arginase expressing cells, but this needs experimental confirmation in VL. Solid lines indicate known mechanistic interactions; dashed lines represent suppositional interactions. Only key shared signaling proteins are included in the model.