Indoleamine 2,3-dioxygenase 1 in corneal endothelial cells limits herpes simplex virus type 1-induced acquired immune response
Indoleamine 2,3-dioxygenase 1 in corneal endothelial cells limits herpes simplex virus type 1-induced acquired immune response
复制标题
DOI：
10.1136/bjophthalmol-2015-306863
复制
发表时间：
2015-10-01
影响因子：
4.1
通讯作者：
Inoue, Yoshitsugu
中科院分区：
文献类型：
--
作者：
Haruki, Tomoko;Miyazaki, Dai;Inoue, Yoshitsugu
背景：角膜内皮细胞是单纯疱疹病毒1型(HSV-1)感染的靶细胞，但HSV感染内皮细胞的发病机制尚未明确。本研究的目的是研究一种未知的角膜内皮细胞保护自身免受HSV-1感染的策略。利用实时定量聚合酶链式反应和免疫印迹技术检测吲哚胺2，3-双加氧酶1(IDO1)的表达。为了检验IDO1是否具有抗病毒作用，我们测试了是否通过阻断IDO1的活性来影响病毒复制。分析IDO1的免疫调节作用，以确定IDO1是否参与了HSV-1致敏的CD4(+)T细胞的回忆反应。阻断IDO1并没有显著限制病毒的转录或复制，这与之前公认的IDO1的抗病毒作用相反。当检测HCEn细胞的抗原提呈功能时，HSV-1免疫的HCEn细胞刺激同种异体CD4(+)T细胞的增殖和IL-10的分泌。当用混合淋巴细胞反应检测HSV-1的召回反应时，HCEn刺激的CD4(+)T细胞调节和限制了召回反应。当在HCEn细胞中沉默IDO1时，HCEn介导的免疫调节活性和调节性T细胞激活降低。结论HSV-1感染诱导的IDO1抑制角膜内皮细胞过度获得性免疫反应，抑制过度获得性免疫反应。
Background Corneal endothelial cells are known to be targets of herpes simplex virus type 1 (HSV-1) infection; however, the pathogenesis of HSV infections of the endothelial cells has not been definitively determined. The purpose of this study was to examine an unrecognised strategy of corneal endothelial cells to protect themselves from HSV-1 infection.Methods Immortalised human corneal endothelial cells (HCEn) were infected with HSV-1. Based on the global transcriptional profile, the expression of indoleamine 2,3-dioxygenase 1 (IDO1) was determined using real-time PCR and western blots. To examine whether IDO1 has any antiviral role, we tested whether viral replication was affected by blocking the activity of IDO1. The immune modulatory role of IDO1 was analysed to determine whether IDO1 might contribute to modulating the recall responses of HSV-1-sensitised CD4(+) T cells.Results IDO1 was strongly expressed in HCEn cells after HSV-1 infection. IDO1 blockade did not significantly restrict viral transcription or replication, arguing against a previously recognised antiviral role for IDO1. When HCEn cells were examined for antigen-presenting function, HSV-1-primed HCEn cells stimulated the proliferation of allogeneic CD4(+) T cells and interleukin 10 (IL-10) secretion. When the recall response to HSV-1 was measured by the mixed lymphocyte reaction, the HCEn-stimulated CD4(+) T cells modulated and limited the recall response. When IDO1 was silenced in HCEn cells, the HCEn-mediated immune modulatory activity and regulatory T-cell activation were reduced. Overexpression of IDO1 promoted immune modulatory activity, which was partly conveyed by IL-10.Conclusions IDO1 induced by HSV-1 infection limits and dampens excessive acquired immune responses in corneal endothelial cells.