title: Candida albicans dampens host defense by downregulating IL-17 production.
abstract: IL-17 is one of the key cytokines that stimulate host defense during a Candida infection. Several studies have demonstrated the capacity of Candida albicans to induce a Th17 response. Surprisingly, experiments employing live C. ablicans demonstrated a specific downregulation of host IL-17 secretion in human blood mononuclear cells (PBMCs). By avoiding the direct contact of live C. albicans and PBMCs, we demonstrate that this inhibition effect is mediated by a soluble factor released by live C. albicans. However, this effect is due neither to the releasing of C. albicans pathogen-associated molecular patterns nor to the alteration of different Th cell subtypes. Rather, we found that live C. albicans shifts tryptophan metabolism by inhibiting IDO expression away from kynurenines and toward 5-hydroxytryptophan metabolites. In addition, we show that these latter 5-hydroxytryptophan metabolites inhibit IL-17 production. In conclusion, live C. albicans inhibits host Th17 responses by modulatory effects on tryptophan metabolism.
authors.affiliation: Department of Medicine, Radboud University Nijmegen Medical Center and Nijmegen Institute for Infection, Inflammation and Immunity, Nijmegen, The Netherlands.
authors.forename: Shih-Chin
authors.initials: SC
authors.lastname: Cheng
authors.forename: Frank
authors.initials: F
authors.lastname: van de Veerdonk
authors.forename: Sanne
authors.initials: S
authors.lastname: Smeekens
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.forename: Jos W M
authors.initials: JW
authors.lastname: van der Meer
authors.forename: Bart-Jan
authors.initials: BJ
authors.lastname: Kullberg
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
mesh_terms: D006916:5-Hydroxytryptophan / Q000378:metabolism; D002176:Candida albicans / Q000276:immunology* / Q000502:physiology; D002478:Cells, Cultured; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D054884:Host-Pathogen Interactions / Q000276:immunology; D006358:Hot Temperature; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D007737:Kynurenine / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014364:Tryptophan / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D020381:Interleukin-17; D053583:Interleukin-1beta; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D007737:Kynurenine; D014364:Tryptophan; D006916:5-Hydroxytryptophan; D014365:Tryptophan Hydroxylase