The mechanism of interferon-gamma induced anti Toxoplasma gondii by indoleamine 2,3-dioxygenase and/or inducible nitric oxide synthase vary among tissues

Suwako Fujigaki, Masao Takemura, Hidetsugu Hamakawa, Mitsuru Seishima, Kuniaki Saito

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L-Tryptophan degradation by indoleamine 2,3-dioxygenase (IDO) induction and reactive nitrogen intermediates produced by inducible nitric oxide synthase (iNOS) induction are important factors for IFN-γ-induced anti-toxoplasma activities. In the present study, the effects of acute Toxoplasma gondii (T. gondii) infection on IDO and iNOS were investigated using wild-type (WT) and IFN-γ gene-deficient (IFN-γ KO) mice. In the WT C57BL/6J mice, enzyme activities and mRNA levels of IDO in both lung and brain were markedly increased, and lung L-tryptophan concentrations were dramatically decreased following infection. In contrast, these metabolic changes did not occur in infected IFN-γ KO mice. The level of iNOS induction in the infected IFN-γ KO mice was high in lung and low in brain compared to that in infected WT mice. The extent of increased mRNA expression of T. gondii surface antigen gene 2 (SAG2) in lung and brain induced by infection was significantly enhanced in the IFN-γ KO mice compared to that in WT mice. Treatment with N-nitro-L-arginine methyl ester, an iNOS inhibitor, increased the levels of SAG2 mRNA in brain, but not in lung following infection. This in vivo study provides evidence that L-tryptophan depletion caused by T. gondii is directly mediated by IFN-γ in the lung, where iNOS is not induced by IFN-γ. This study suggests that there is an anti-toxoplasma mechanism of cross-regulation between iNOS and IDO and that the expression of main anti-parasite effector mechanisms of iNOS and/or IDO may vary among tissues.

Original languageEnglish
Pages (from-to)97-103
Number of pages7
JournalAdvances in Experimental Medicine and Biology
Publication statusPublished - 01-12-2003


All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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