Interferon Lambda Upregulates IDO1 Expression in Respiratory Epithelial Cells After Influenza Virus Infection
Interferon Lambda Upregulates IDO1 Expression in Respiratory Epithelial Cells After Influenza Virus Infection
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DOI：
10.1089/jir.2014.0052
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发表时间：
2015-07-01
影响因子：
2.3
通讯作者：
Tripp, Ralph A.
中科院分区：
文献类型：
--
作者：
Fox, Julie M.;Crabtree, Jackelyn M.;Tripp, Ralph A.
流感感染导致肺实质中吲哚胺 2, 3-双加氧酶 (IDO) 活性增加。 IDO 将色氨酸分解代谢为犬尿氨酸，导致免疫抑制。多种细胞类型表达IDO，虽然IFN-γ上调树突状细胞和巨噬细胞中的IDO，但尚不清楚流感感染期间呼吸道上皮细胞中IDO如何受到影响。在本研究中，研究了呼吸道上皮细胞流感感染后 IFN-α 在 IDO 调节中的作用。 IDO1 表达与 IFN-表达同时增加。在分化的 NHBE 细胞中，IDO 代谢物在基底外侧释放。重组 IFN- 上调 IDO1 活性，而 IFN- 沉默则降低流感感染期间 IDO1 的表达。在 IFN-刺激期间，大多数分化细胞类型能够表达 IDO，但在流感感染期间，IDO 主要在未感染的细胞中表达。这些研究表明 IDO 在宿主对流感感染的反应中发挥作用，并为增强疫苗反应和治疗方法的新方法提供了见解。
Influenza infection causes an increase in indoleamine 2, 3-dioxygenase (IDO) activity in the lung parenchyma. IDO catabolizes tryptophan into kynurenine, leading to immune dampening. Multiple cell types express IDO, and while IFN- upregulates IDO in dendritic cells and macrophages, it is unclear how IDO is affected in respiratory epithelial cells during influenza infection. In this study, the role of IFN- in IDO regulation was investigated after influenza infection of respiratory epithelial cells. IDO1 expression increased concurrently with IFN- expression. In differentiated NHBE cells, the IDO metabolite was released basolaterally. Recombinant IFN- upregulated IDO1 activity, and silencing of IFN- decreased IDO1 expression during influenza infection. During IFN- stimulation, most differentiated cell types are able to express IDO but during influenza infection, IDO is primarily expressed in uninfected cells. These studies show a role for IDO in the host response to influenza infection, and they provide insights into novel approaches for enhancing vaccine responses and therapeutic approaches.