Candida albicans dampens host defense by downregulating IL-17 production.
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.
Cheng
Shih-Chin
SC
Department of Medicine, Radboud University Nijmegen Medical Center and Nijmegen Institute for Infection, Inflammation and Immunity, Nijmegen, The Netherlands.
van de Veerdonk
Frank
F
Smeekens
Sanne
S
Joosten
Leo A B
LA
van der Meer
Jos W M
JW
Kullberg
Bart-Jan
BJ
Netea
Mihai G
MG
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
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