title: Cytomegalovirus impairs the induction of indoleamine 2,3-dioxygenase mediated antimicrobial and immunoregulatory effects in human fibroblasts.
abstract: Human fibroblasts provide immunosuppressive functions that are partly mediated by the tryptophan-catabolizing enzyme indoleamine-2,3-dioxygenase (IDO). Moreover, upon stimulation with inflammatory cytokines human fibroblasts exhibit broad-spectrum antimicrobial effector functions directed against various clinically relevant pathogens and these effects are also IDO-dependent. Therefore human fibroblasts are suggested to be involved in the control of immune reactions during infectious diseases. As human cytomegalovirus (HCMV) represents a pathogen frequently found in immunocompromised hosts and IDO is involved in the control of HCMV growth, we here investigated the impact of HCMV infection on IDO-mediated antimicrobial and immunoregulatory effects. We show that infection with HCMV substantially impairs IFN-γ-induced IDO-activity in human fibroblasts in a dose and time dependent fashion. Consequently, these cells are no longer able to restrict bacterial and parasitic growth and, furthermore, loose their IDO-mediated immunosuppressive capacity. Our results may have significant implications for the course of HCMV infection during solid organ transplantation: we suggest that loss of IDO-mediated antimicrobial and immunoregulatory functions during a HCMV infection might at least in part explain the enhanced risk of organ rejection and infections observed in patients with HCMV reactivation after solid organ transplantation.
authors.affiliation: Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Heseler
authors.forename: Silvia K
authors.initials: SK
authors.lastname: Schmidt
authors.forename: Katrin
authors.initials: K
authors.lastname: Spekker
authors.forename: Christian
authors.initials: C
authors.lastname: Sinzger
authors.forename: Rüdiger V
authors.initials: RV
authors.lastname: Sorg
authors.forename: Marc
authors.initials: M
authors.lastname: Quambusch
authors.forename: Albert
authors.initials: A
authors.lastname: Zimmermann
authors.forename: Roland
authors.initials: R
authors.lastname: Meisel
authors.forename: Walter
authors.initials: W
authors.lastname: Däubener
mesh_terms: D002460:Cell Line; D003587:Cytomegalovirus / Q000254:growth & development / Q000502:physiology*; D004790:Enzyme Induction; D005347:Fibroblasts / Q000276:immunology*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase