Candida Infection Biology – fungal armoury, battlefields ... - FINSysB

A central role of complement for the Candida albicansinduced
cytokine production by human cells
Shih-Chin Cheng 1,2 , Tom Sprong 1,2 , Leo A.B. Joosten 1,2 , Jos W.M. van der
Meer 1,2 , Bart-Jan Kullberg 1,2 , Bernhard Hube 3,4 , Lone Schejbel 5 , Peter
Garred 5 Marcel van Deuren 1,2 , Mihai G. Netea 1,2
1 Departments of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, the
Netherlands; 2 Nijmegen Institute for Infection, Inflammation and Immunity (N4i), Nijmegen,
the Netherlands; 3 Department of Microbial Pathogenicity Mechanism, Leibniz Institute for
Natural Product Research and Infection Biology - Hans Knoell Institute, Jena, Germany;
4 Friedrich Schiller University, Jena, Germany; 5 Department of Clinical Immunology, Laboratory
of Molecular Medicine, Rigshospitalet, Copenhagen, Denmark.
In experimental studies, the role of complement for antifungal host defense has
been attributed to its ability of opsonization. In this study we report that in humans
an activated complement system mainly augments Candida albicans-induced host
pro-inflammatory cytokine production via C5a-C5a receptor signaling, while
Candida phagocytosis and intracellular killing is not influenced. By blocking the
C5a-C5aR signaling pathway either with anti-C5a antagonist antibodies or with the
C5aR antagonist W-54001, C. albicans-induced IL-6 and IL-1 levels were
significantly reduced. Recombinant C5a augmented cytokine production. In
addition, using serum from patients with various complement deficiencies, we
demonstrate a crucial role of C5, but not C6 or the membrane attack complex, for
C. albicans-induced IL-6 and IL-1 in monocytes. These findings reveal a central
role of anaphylatoxin C5a in augmenting host pro-inflammatory cytokine production
upon contact with C. albicans, and defines the role of the complement system for
anti-Candida host defense in humans.
We are grateful to the European Commission for funding the FINSysB Marie Curie Initial Training Network
(PITN-GA-2008-214004).
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