title: Complement plays a central role in Candida albicans-induced cytokine production by human PBMCs.
abstract: In experimental studies, the role of complement in antifungal host defense has been attributed to its opsonizing capability. In this study, we report that in humans an activated complement system mainly augments Candida albicans-induced host proinflammatory cytokine production via C5a-C5aR signaling, while phagocytosis and intracellular killing of Candida are 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-1β levels were significantly reduced. Recombinant C5a augmented cytokine production. In addition, using serum from patients with various complement deficiencies, we demonstrated a crucial role of C5, but not C6 or the membrane attack complex, in C. albicans-induced IL-6 and IL-1β production in monocytes. These findings reveal a central role of anaphylatoxin C5a in augmenting host proinflammatory cytokine production upon contact with C. albicans, and define the role of the complement system in anti-Candida host defense in humans.
authors.affiliation: Department of Medicine, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Shih-Chin
authors.initials: SC
authors.lastname: Cheng
authors.forename: Tom
authors.initials: T
authors.lastname: Sprong
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.forename: Jos W M
authors.initials: JW
authors.lastname: van der Meer
authors.forename: Bart-Jan
authors.initials: BJ
authors.lastname: Kullberg
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hube
authors.forename: Lone
authors.initials: L
authors.lastname: Schejbel
authors.forename: Peter
authors.initials: P
authors.lastname: Garred
authors.forename: Marcel
authors.initials: M
authors.lastname: van Deuren
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
mesh_terms: D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology*; D003167:Complement Activation / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology*; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology*; D015850:Interleukin-6 / Q000276:immunology*; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology; D015398:Signal Transduction / Q000276:immunology
chemical_list: C508585:IL1B protein, human; C508600:IL6 protein, human; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D003165:Complement System Proteins