HUMAN INDOLEAMINE 2,3-DIOXYGENASE INHIBITS TOXOPLASMA-GONDII GROWTH IN FIBROBLAST CELLS

Interferon-gamma (IFN-gamma) is known to inhibit the growth of Toxopla sma gondii both in vivo and in vitro. The IFN-gamma induced anti-toxop lasma activity in human cells is strongly correlated with the degradat ion of the essential amino acid L-tryptophan in vitro. Destruction of L-tryptophan is due to an increased activity of indoleamine 2,3-dioxyg enase (IDO), which is transcriptionally activated by IFN-gamma. To det ermine if indoleamine 2,3-dioxygenase alone is sufficient to block the T. gondii growth, we transfected human fibroblast cells with an IDO c DNA expression plasmid using a metallothionein-inducible promoter. We showed that IDO mRNA and its enzymatic activity are inducible in fibro blast cells transfected with right-orientation IDO cDNA upon addition of CdCl2 to culture medium. The elevated IDO enzyme activity is strong ly correlated with an inhibition of T. gondii growth. No IDO mRNA nor enzyme activity is induced by CdCl2 in reverse orientation transfected cells, and no adverse effects were observed on T. gondii growth in ce lls transfected with the reverse IDO-construct or in control parent ce lls with or without supplementation of CdCl2. Our observations along w ith the recent report by Habara-Ohkubo et al. (Infect. Immun. 61, 1810 -1813, 1993) suggest that IFN-gamma-induced antitoxoplasma activity is due at least in part to the activation of IDO gene.