IAI Accepts, published online ahead of print on 26 October 2009

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Infect. Immun. doi:10.1128/IAI.01041-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Candida albicans releases soluble factors that potentiate cytokine production by human cells through a PAR1/PAR2-independent pathway

SHIH-CHIN CHENG, LOUIS Y.A. CHAI, LEO A.B. JOOSTEN, ANNA VECCHIARELLI, BERNHARD HUBE, JOS W.M. VAN DER MEER, BART JAN KULLBERG, and MIHAI G. NETEA^*

Departments of Medicine, Radboud University Nijmegen Medical Center, Nijmegen and Nijmegen Institute for Infection, Inflammation and Immunity (N4i), P.O Box 9101, Geert Grootplein, 6525 GA, Nijmegen, The Netherlands; Department of Experimental Medicine, Università degli Studi di Perugia, Italy; Department of Microbial Pathogenicity Mechanism, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knoell Institute, Jena, Germany

^* To whom correspondence should be addressed. Email: M.Netea{at}aig.umcn.nl.

The innate immune system recognizes Pathogen-Associated Molecular Patterns (PAMPs) through Pattern Recognition Receptors (PRR) and transduces downstream signaling to activate host defense. Here we report that in addition to direct PAMP-PRR interaction, live C. albicans can release soluble factors to actively potentiate IL-6 and IL-8 production induced in human mononuclear cells by the fungi. Although PAR1 (Protease-Activated Receptor 1) and PAR2 ligation can moderately upregulate TLR4-mediated IL-8 production, no effect on C. albicans-induced cytokine was apparent. Similarly, the blockade of PAR signaling did not reverse the potentiation of cytokine production induced by soluble factors released by C. albicans. In conclusion, C. albicans releases soluble factors that potentiate cytokine release in a PAR1/2-independent manner. Thus, human PAR1 and PAR2 have a redundant role for the activation of human cells by C. albicans.