Indoleamine 2,3-Dioxygenase Is Involved in the Inflammation Response of Corneal Epithelial Cells to Aspergillus fumigatus Infections.
Indoleamine 2,3-Dioxygenase Is Involved in the Inflammation Response of Corneal Epithelial Cells to Aspergillus fumigatus Infections.
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吲哚胺2,3-双加氧酶参与角膜上皮细胞对烟曲霉感染的炎症反应
DOI：
10.1371/journal.pone.0137423
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Peng X
中科院分区：
文献类型：
--
作者：
Jiang N;Zhao G;Lin J;Hu L;Che C;Li C;Wang Q;Xu Q;Peng X
吲哚胺2，3-双加氧酶（Indoleamine 2，3-dioxygenase，IDO）主要在活化的树突状细胞中表达，是免疫应答的调节因子。然而，IDO在抗真菌角膜感染的免疫应答中的作用尚未研究。为了评估IDO在真菌炎症中的调节机制，我们求助于人角膜上皮细胞（HCECs），其被称为角膜对抗病原微生物的第一屏障。我们发现IDO在烟曲霉感染的角膜上皮中显著上调（A. fumigatus）和与A.烟熏。IDO抑制剂1-甲基色氨酸（1-methyltryptophan，1-MT）可增强A.烟曲霉孢子感染Dectin-1作为一种重要的C型凝集素受体，可识别β-葡聚糖，介导真菌天然免疫应答。在本研究中，与A.烟熏刺激而Dectin-1特异性抑制剂海带多糖则部分抑制A.烟熏。进一步的研究表明，IDO活性的抑制放大了由Dectin-1激活诱导的炎性细胞因子IL-1β和IL-6的表达。提示IDO参与了真菌性角膜炎的免疫反应。Dectin-1的激活可能与A.烟曲霉孢子诱导的IDO上调。
Indoleamine 2,3-dioxygenase (IDO), which is mainly expressed in activated dendritic cells, is known as a regulator of immune responses. However, the role of IDO in immune responses against fungal corneal infection has not been investigated. To evaluate the regulatory mechanisms of IDO in fungal inflammation, we resorted to human corneal epithelial cells (HCECs), known as the first barrier of cornea against pathogenic microorganisms. We found that IDO was significantly up-regulated in corneal epithelium infected with Aspergillus fumigatus (A. fumigatus) and HCECs incubated with spores of A. fumigatus. Furthermore, IDO inhibitor (1-methyltryptophan, 1-MT) enhanced inflammatory cytokines IL-1β and IL-6 expression which were up-regulated by A. fumigatus spores infection. Dectin-1, as one of the important C-type lectin receptors, can identify β-glucan, and mediate fungal innate immune responses. In the present study, pre-treatment with curdlan, a Dectin-1 agonist, further enhanced IDO expression compared with A. fumigatus stimulation. While laminarin, the Dectin-1 specific inhibitor, partially inhibited IDO expression stimulated by A. fumigatus. Further studies demonstrated inhibition of IDO activity amplified the expressions of inflammatory cytokines IL-1β and IL-6 induced by activation of Dectin-1. These results suggested that IDO was involved in the immune responses of fungal keratitis. The activation of Dectin-1 may contribute to A. fumigatus spores-induced up-regulation of IDO.