Expression of indoleamine 2,3-dioxygenase, tryptophan degradation, and kynurenine formation during in vivo infection with Toxoplasma gondii:: Induction by endogenous gamma interferon and requirement of interferon regulatory factor 1
Expression of indoleamine 2,3-dioxygenase, tryptophan degradation, and kynurenine formation during in vivo infection with Toxoplasma gondii:: Induction by endogenous gamma interferon and requirement of interferon regulatory factor 1
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DOI：
10.1128/iai.70.2.859-868.2002
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发表时间：
2002-02-01
影响因子：
3.1
通讯作者：
Gazzinelli, RT
中科院分区：
文献类型：
--
作者：
Silva, NM;Rodrigues, CV;Gazzinelli, RT
研究了弓形虫体内感染诱导吲哚胺2，3-双加氧酶（indoleamine 2，3-dioxygenase，INDO）表达及色氨酸（Trp）-犬尿氨酸（kynurenine，Kyn）代谢途径。在感染T.刚地在感染后10 - 20天，在肺中检测到最大的INDO mRNA表达和酶活性。此外，在IFN-γ（IFN-γ（-/-））或IFN调节因子-1（IRF-1（-/-））缺陷小鼠的组织中完全不存在INDO mRNA表达、Trp降解和Kyn形成的诱导。这些发现表明，在T.刚地相反，INDO mRNA的表达及其活性在TNF受体、p55或诱导型一氧化氮合酶缺陷小鼠感染T.刚地结合IFN-γ（-/-）和IRF-1（-/-）小鼠对T.我们的研究结果表明，可能参与INDO和色氨酸降解宿主抵抗这种寄生虫的早期感染。
The induction of indoleamine 2,3-dioxygenase (INDO) expression and the tryptophan (Trp)-kynurenine (Kyn) metabolic pathway during in vivo, infection with Toxoplasma gondii was investigated. Decreased levels of Trp and increased formation of Kyn were observed in the lungs, brain, and serum from mice infected with T. gondii. Maximal INDO mRNA expression and enzyme activity were detected in the lungs at 10 to 20 days postinfection. Further, the induction of INDO mRNA expression, Trp degradation and Kyn formation were completely absent in tissues from mice deficient in IFN-gamma (IFN-gamma(-/-)) or IFN regulatory factor -1 (IRF-1(-/-)). These findings indicate the important role of endogenous IFN-gamma and IRF-1 in the in vivo induction of the Trp-Kyn metabolic pathway during acute infection with T. gondii. In contrast, expression of INDO mRNA and its activity was preserved in the tissues of TNF-receptor, p55- or inducible nitric oxide synthase-deficient mice infected with T. gondii. Together with the results showing the extreme susceptibility of the IFN-gamma(-/-) and the IRF-1(-/-) mice to infection with T. gondii, our results indicate a possible involvement of INDO and Trp degradation in host resistance to early infection with this parasite.