title: Indoleamine 2,3-dioxygenase activity is associated with regulatory T cell response in acute Puumala hantavirus infection.
abstract: High indoleamine 2,3-dioxygenase (IDO) activity is associated with clinically severe acute infection caused by Puumala hantavirus. The immunoregulatory effects of IDO can be mediated either through metabolic control of effector T cells, caused by depletion of the essential amino acid tryptophan, or intercellular signaling and activation of regulatory T cell responses. Here, we have studied 24 patients with acute Puumala hantavirus infection to distinguish between these possibilities. Maximum IDO activity showed a significant positive correlation with FOXP3 expression levels in regulatory T cells, a quantitative surrogate marker for suppressive capability. In contrast, IDO activity did not correlate with the frequency of CD8+effector cells in cell cycle. The data suggest that in Puumala infection, the mechanism responsible for the suppressive effect of IDO is not metabolic control of effector cells but rather the signaling mediated by tryptophan breakdown products, such as kynurenine.
authors.affiliation: Department of Immunology, Medicum, University of Helsinki, 00290 Helsinki, Finland.|Research Programs Unit, Immunobiology, University of Helsinki, 00290 Helsinki, Finland.
authors.forename: Tuisku-Tuulia
authors.initials: TT
authors.lastname: Koivula
authors.affiliation: Department of Immunology, Medicum, University of Helsinki, 00290 Helsinki, Finland.|Research Programs Unit, Immunobiology, University of Helsinki, 00290 Helsinki, Finland.
authors.forename: Anni
authors.initials: A
authors.lastname: Tuulasvaara
authors.affiliation: Department of Immunology, Medicum, University of Helsinki, 00290 Helsinki, Finland.|Research Programs Unit, Immunobiology, University of Helsinki, 00290 Helsinki, Finland.
authors.forename: Iivo
authors.initials: I
authors.lastname: Hetemäki
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, University of Tampere, 33014 Tampere, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Hurme
authors.affiliation: Department of Medicine, School of Medicine, University of Tampere, 33014 Tampere, Finland.|Department of Internal Medicine, Tampere University Hospital, 33014, Tampere, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Mäkelä
authors.affiliation: Department of Medicine, School of Medicine, University of Tampere, 33014 Tampere, Finland.|Department of Internal Medicine, Tampere University Hospital, 33014, Tampere, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Mustonen
authors.affiliation: Department of Virology, Medicum, University of Helsinki, 00290 Helsinki, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Vaheri
authors.affiliation: Department of Immunology, Medicum, University of Helsinki, 00290 Helsinki, Finland petteri.arstila@helsinki.fi.|Research Programs Unit, Immunobiology, University of Helsinki, 00290 Helsinki, Finland.
authors.forename: T Petteri
authors.initials: TP
authors.lastname: Arstila
mesh_terms: D015415:Biomarkers; D004789:Enzyme Activation; D018778:Hantavirus Infections / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D029262:Puumala virus / Q000276:immunology*; D012720:Severity of Illness Index; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase
keywords: IDO; T cell; hantavirus; immunoregulation; tryptophan