Complement plays a central role in Candida albicans-induced cytokine production by human PBMCs
Complement plays a central role in Candida albicans-induced cytokine production by human PBMCs
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DOI：
10.1002/eji.201142057
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发表时间：
2012-04-01
影响因子：
5.4
通讯作者：
Netea, Mihai G.
中科院分区：
文献类型：
--
作者：
Cheng, Shih-Chin;Sprong, Tom;Netea, Mihai G.
在实验研究中，补体在抗真菌宿主防御中的作用归因于其调理能力。在这项研究中，我们报告说，在人类激活的补体系统主要是通过C5 a-C5 aR信号增强白念珠菌诱导的宿主促炎细胞因子的产生，而念珠菌的吞噬作用和细胞内杀伤不受影响。通过用抗C5 a拮抗剂抗体或C5 aR拮抗剂W-54001阻断C5 a-C5 aR信号传导途径，C.白色念珠菌诱导的IL-6和IL-1 β水平显著降低。重组C5 a增强细胞因子的产生。此外，使用各种补体缺乏患者的血清，我们证明了C5在C中的关键作用，而不是C6或膜攻击复合物。白念珠菌诱导单核细胞产生IL-6和IL-1 β。这些发现揭示了过敏毒素C5 a在与C.白色念珠菌，并确定补体系统在人类抗念珠菌宿主防御中的作用。
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.