Open AccessCandida albicans Dampens Host Defense by Downregulating IL-17 Production
Author(s) -
ShihChin Cheng,
Frank L. van de Veerdonk,
Sanne P. Smeekens,
Leo A. B. Joosten,
J.W.M. van der Meer,
Bart Jan Kullberg,
Mihai G. Netea
Publication year - 2010
Publication title -
the journal of immunology
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.1000756
Subject(s) - candida albicans , corpus albicans , peripheral blood mononuclear cell , microbiology and biotechnology , pathogen , downregulation and upregulation , biology , secretion , tryptophan , host (biology) , chemistry , biochemistry , in vitro , gene , genetics , amino acid
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.
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