The Absence of IDO Upregulates Type I IFN Production, Resulting in Suppression of Viral Replication in the Retrovirus-Infected Mouse
The Absence of IDO Upregulates Type I IFN Production, Resulting in Suppression of Viral Replication in the Retrovirus-Infected Mouse
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DOI：
10.4049/jimmunol.0901150
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发表时间：
2010-09-15
影响因子：
4.4
通讯作者：
Seishima, Mitsuru
中科院分区：
文献类型：
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作者：
Hoshi, Masato;Saito, Kuniaki;Seishima, Mitsuru
吲哚胺2，3-双加氧酶，L-色氨酸降解酶，在对几种不同类型细胞的强大免疫调节作用中起关键作用。由于病毒感染后IDO活性的调节可能对疾病进展有很大影响，我们研究了IDO在LP-BM 5小鼠白血病病毒感染后的作用。我们发现，与野生型（WT）小鼠相比，IDO敲除（IDO-/-）和1-甲基-D-L-色氨酸处理的小鼠脾脏中BM 5前病毒拷贝数受到抑制，I型IFN增加。此外，IDO-/-小鼠中浆细胞样树突状细胞的数量在前者中高于WT小鼠。此外，IDO-/-小鼠中I型IFN的中和导致LP-BM 5病毒复制增加。此外，IDO-/-小鼠或1-甲基-D-L-色氨酸处理的小鼠单独感染LP-BM 5或同时感染弓形虫和LP-BM 5的存活率明显高于WT小鼠的存活率。据我们所知，本研究是第一份报告，观察抑制病毒复制与上调I型干扰素在IDO-/-小鼠，这表明IDO途径的调制可能是一种有效的策略，用于治疗病毒感染。免疫学杂志，2010，185：3305-3312。
Indoleamine 2,3-dioxygenase, the L-tryptophan-degrading enzyme, plays a key role in the powerful immunomodulatory effects on several different types of cells. Because modulation of IDO activities after viral infection may have great impact on disease progression, we investigated the role of IDO following infection with LP-BM5 murine leukemia virus. We found suppressed BM5 provirus copies and increased type I IFNs in the spleen from IDO knockout (IDO-/-) and 1-methyl-D-L-tryptophan-treated mice compared with those from wild-type (WT) mice. Additionally, the number of plasmacytoid dendritic cells in IDO-/- mice was higher in the former than in the WT mice. In addition, neutralization of type I IFNs in IDO-/- mice resulted in an increase in LP-BM5 viral replication. Moreover, the survival rate of IDO-/- mice or 1-methyl-D-L-tryptophan-treated mice infected with LP-BM5 alone or with both Toxoplasma gondii and LP-BM5 was clearly greater than the survival rate of WT mice. To our knowledge, the present study is the first report to observe suppressed virus replication with upregulated type I IFN in IDO-/- mice, suggesting that modulation of the IDO pathway may be an effective strategy for treatment of virus infection. The Journal of Immunology, 2010, 185: 3305-3312.