Complement plays a central role in Candida albicans-induced cytokine production by human PBMCs

被引：56

作者：

Cheng, Shih-Chin ^{[1
,2
]}

Sprong, Tom ^{[1
,2
]}

Joosten, Leo A. B. ^{[1
,2
]}

van der Meer, Jos W. M. ^{[1
,2
]}

Kullberg, Bart-Jan ^{[1
,2
]}

Hube, Bernhard ^{[3
,4
]}

Schejbel, Lone ^{[5
]}

Garred, Peter ^{[5
]}

van Deuren, Marcel ^{[1
,2
]}

Netea, Mihai G. ^{[1
,2
]}

机构：

[1] Radboud Univ Nijmegen, Med Ctr, Dept Med, NL-6525 ED Nijmegen, Netherlands

[2] N4i, Nijmegen, Netherlands

[3] Hans Knoell Inst, Leibniz Inst Nat Prod Res & Infect Biol, Dept Microbial Pathogen Mech, Jena, Germany

[4] Univ Jena, Jena, Germany

[5] Rigshosp, Mol Med Lab, Dept Clin Immunol, DK-2100 Copenhagen, Denmark

来源：

EUROPEAN JOURNAL OF IMMUNOLOGY | 2012年 / 42卷 / 04期

基金：

欧盟第七框架计划;

关键词：

Candida; Complement; C5a; IL-6; IL-1; ss; IMMUNOGLOBULIN-G ANTIBODIES; MANNOSE-BINDING LECTIN; WHOLE-BLOOD MODEL; INFLAMMATORY RESPONSES; FUNGAL-INFECTIONS; C5A RECEPTOR; PATHWAY INITIATION; SEPSIS SYNDROME; HOST-DEFENSE; C3; BINDING;

D O I：

10.1002/eji.201142057

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

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-1 beta 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-1 beta 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.

引用

页码：993 / 1004

页数：12

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