Dectin-1 stimulation by Candida albicans yeast or zymosan triggers NFAT activation in macrophages and dendritic cells
Dectin-1 stimulation by Candida albicans yeast or zymosan triggers NFAT activation in macrophages and dendritic cells
复制标题
DOI：
10.4049/jimmunol.178.5.3107
复制
发表时间：
2007-03-01
影响因子：
4.4
通讯作者：
Underhill, David M.
中科院分区：
文献类型：
--
作者：
Goodridge, Helen S.;Simmons, Randi M.;Underhill, David M.
先天免疫模式识别受体在病原体检测和抗菌素反应的启动中起着关键作用。我们和其他人之前已经证明了p -葡聚糖受体Dectin-1在巨噬细胞和树突状细胞识别致病真菌中的重要性，并阐明了Dectin-1信号协调抗真菌反应的一些机制。虽然单独的Dectin-1信号足以触发吞噬和src - syk介导的抗菌活性氧的诱导，但与TLR2信号的合作可增强NF-kappa B的激活并调节细胞因子的产生。在这项研究中，我们证明了Dectin-1信号也可以通过激活NFAT直接调节基因表达。酵素颗粒或活的白色念珠菌酵母菌连接Dectin-1可触发巨噬细胞和树突状细胞中的NFAT激活。dectin -1触发的NFAT激活在诱导早期生长反应2和早期生长反应3转录因子以及环氧化酶-2中起作用。此外，我们发现NFAT激活调节酶酶酶刺激的树突状细胞产生IL-2、IL-10和il - 12p70。这些数据证实了NFAT在髓细胞中的激活是一种调节先天抗菌反应的新机制。
Innate immune pattern recognition receptors play critical roles in pathogen detection and initiation of antimicrobial responses. We and others have previously demonstrated the importance of the P-glucan receptor Dectin-1 in the recognition of pathogenic fungi by macrophages and dendritic cells and have elucidated some of the mechanisms by which Dectin-1 signals to coordinate the antifungal response. While Dectin-1 signals alone are sufficient to trigger phagocytosis and Src-Syk-mediated induction of antimicrobial reactive oxygen species, collaboration with TLR2 signaling enhances NF-kappa B activation and regulates cytokine production. In this study we demonstrate that Dectin-1 signaling can also directly modulate gene expression via activation of NFAT. Dectin-1 ligation by zymosan particles or live Candida albicans yeast triggers NFAT activation in macrophages and dendritic cells. Dectin-1-triggered NFAT activation plays a role in the induction of early growth response 2 and early growth response 3 transcription factors, and cyclooxygenase-2. Furthermore, we show that NFAT activation regulates IL-2, IL-10 and IL-12 p70 production by zymosan-stimulated dendritic cells. These data establish NFAT activation in myeloid cells as a novel mechanism of regulation of the innate antimicrobial response.