Trypanosoma cruzi Evades the Protective Role of Interferon-Gamma-Signaling in Parasite-Infected Cells
Figure 4
STAT1-regulated expression of ido is involved in the control of T. cruzi infection.
(A,B) Exposure of cells to the JAK inhibitor AG-490 resulted in decreased STAT1 phosphorylation both at tyrosine residue 701 and serine residue 727 and is associated with a reduced intracellular STAT1 expression. Equal numbers of HFF and A549 cells were either pre-treated with 5 ng/ml of IFNγ or challenged for 18 h with parasites at an MOI of 15, in the absence or presence of AG-490 (50 µM). Representative Western blot results (A) and the corresponding quantification of STAT1 expression (B) are shown (n = 4). (C,D) Stimulation of HFF cells with IFNγ leads to increased enzymatic activity of indoleamine 2,3-dioxygenase (IDO, C) and elevated NO production (D), as measured with Ehrlich and Griess reagent, respectively (n = 3 in triplicate). (E) Inhibition of IDO by 1-methyltryptophan (1-MT, 1.5 mM) or iNOS by S-methylisothiourea sulfate (SMT, 1 mM) in IFNγ-pre-treated HFF cells resulted in significantly elevated numbers of T. cruzi-replicating cells (n = 4 in triplicate).