Figure 1.

Intracellular trypanosomatid parasites evade the protective role of IFNγ signaling by targeting essential components of the JAK-STAT pathway. Gene induction by serine(SP)- and tyrosine(YP)-phosphorylated STAT1 including interferon-regulatory factor 1 (IRF1), inducible NO synthase (iNOS) and STAT1 is crucial for the anti-parasite actions of this pathway. The model depicts the inhibition of STAT1 transcriptional activity by parasite-mediated dephosphorylation of STAT1 serine 727 (as shown for T. cruzi.²³) and activation of the protein tyrosine phosphatase SHP1 (in L. donovani-infected cells⁵¹).