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Candida albicans Dampens Host Defense by Downregulating IL-17 Production

Shih-Chin Cheng, Frank van de Veerdonk, Sanne Smeekens, Leo A. B. Joosten, Jos W. M. van der Meer, Bart-Jan Kullberg and Mihai G. Netea
J Immunol August 15, 2010, 185 (4) 2450-2457; DOI: https://doi.org/10.4049/jimmunol.1000756
Shih-Chin Cheng
Department of Medicine, Radboud University Nijmegen Medical Center and
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Frank van de Veerdonk
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Sanne Smeekens
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Leo A. B. Joosten
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Jos W. M. van der Meer
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Bart-Jan Kullberg
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Mihai G. Netea
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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.

Footnotes

  • This work was supported by Grant PITN-GA-2008-214004 from the EU-FP7 FINSysB Marie Curie Initial Training Network (to S.-C.C.) and by a Vici Grant from the Netherlands Organization for Scientific Research (to M.G.N.).

  • Abbreviations used in this paper:

    IL-1β
    β form of pro–IL-1
    LDH
    lactase dehydrogenase
    MR
    mannose receptor
    PAMP
    pathogen-associated molecular pattern
    PRR
    pattern recognition receptor
    RORγt
    retinoic acid-related orphan receptor γt
    Sap
    secreted aspartic protease.

  • Received March 5, 2010.
  • Accepted June 12, 2010.
  • Copyright © 2010 by The American Association of Immunologists, Inc.
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The Journal of Immunology: 185 (4)
The Journal of Immunology
Vol. 185, Issue 4
15 Aug 2010
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Candida albicans Dampens Host Defense by Downregulating IL-17 Production
Shih-Chin Cheng, Frank van de Veerdonk, Sanne Smeekens, Leo A. B. Joosten, Jos W. M. van der Meer, Bart-Jan Kullberg, Mihai G. Netea
The Journal of Immunology August 15, 2010, 185 (4) 2450-2457; DOI: 10.4049/jimmunol.1000756

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Candida albicans Dampens Host Defense by Downregulating IL-17 Production
Shih-Chin Cheng, Frank van de Veerdonk, Sanne Smeekens, Leo A. B. Joosten, Jos W. M. van der Meer, Bart-Jan Kullberg, Mihai G. Netea
The Journal of Immunology August 15, 2010, 185 (4) 2450-2457; DOI: 10.4049/jimmunol.1000756
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