title: Indoleamine 2,3-dioxygenase 1 in corneal endothelial cells limits herpes simplex virus type 1-induced acquired immune response.
abstract: 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.
authors.affiliation: Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Haruki
authors.affiliation: Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Miyazaki
authors.affiliation: Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Koudai
authors.initials: K
authors.lastname: Inata
authors.affiliation: Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Sasaki
authors.affiliation: Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Yukimi
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Kandori
authors.affiliation: Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Yakura
authors.affiliation: Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Noguchi
authors.affiliation: Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Chizu
authors.initials: C
authors.lastname: Touge
authors.affiliation: Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Ishikura
authors.affiliation: Division of Medical Oncology and Respirology, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Touge
authors.affiliation: Corneal Transplantation Section, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamagami
authors.affiliation: Division of Ophthalmology and Visual Science, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Inoue
mesh_terms: D017951:Antigen Presentation / Q000276:immunology; D015153:Blotting, Western; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics*; D004728:Endothelium, Corneal / Q000201:enzymology* / Q000276:immunology / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D018259:Herpesvirus 1, Human / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000096:biosynthesis / Q000235:genetics*; D016849:Keratitis, Herpetic / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D014779:Virus Replication
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D004247:DNA
keywords: Cornea; Infection