Differential use of CARD9 by dectin-1 in macrophages and dendritic cells.
Differential use of CARD9 by dectin-1 in macrophages and dendritic cells.
复制标题
DOI：
10.4049/jimmunol.182.2.1146
复制
发表时间：
2009-01-15
期刊：
影响因子：
--
通讯作者：
Underhill DM
中科院分区：
文献类型：
--
作者：
Goodridge HS;Shimada T;Wolf AJ;Hsu YM;Becker CA;Lin X;Underhill DM
模式识别受体Toll样受体2（TLR 2）和Dectin-1在协调巨噬细胞和树突状细胞（DC）对真菌的反应中起关键作用。促炎细胞因子的诱导由来自TLR 2和Dectin-1的信号指示。最近的报道鉴定了CARD 9在先天性抗真菌应答中的作用，证明了CARD 9-Bcl 10介导的NF-κB活化和通过Dectin-1刺激的鼠骨髓来源的DC（bmDC）中的促炎细胞因子诱导。我们现在报道，Dectin-1-CARD 9信号不能激活NF-κB并驱动小鼠骨髓源性巨噬细胞（bmM）中的TNF-α诱导。然而，用GM-CSF或IFN-γ引发bmM允许Dectin-1-CARD 9介导的TNF-α诱导。对其他巨噬细胞/DC群体的分析揭示了Dectin-1-CARD 9信号传导驱动TNF-α产生的能力的进一步变化。常驻腹膜细胞和肺泡巨噬细胞在Dectin-1连接后产生TNF-α，而巯基乙酸盐诱导的腹膜巨噬细胞和Flt 3L衍生的DC不产生TNF-α。我们目前的数据表明，CARD 9通过其CARD结构域被招募到吞噬体，在那里它甚至在Dectin-1不足以驱动细胞因子产生的细胞中增强TLR诱导的细胞因子产生。在这样的细胞中，Dectin-1、CARD 9和Bcl 10水平不是限制性的，并且数据表明这些细胞表达限制Dectin-1-CARD 9信号传导用于TNF-α诱导的额外因子。
The pattern recognition receptors Toll-like receptor 2 (TLR2) and Dectin-1 play key roles in coordinating the responses of macrophages and dendritic cells (DC) to fungi. Induction of pro-inflammatory cytokines is instructed by signals from both TLR2 and Dectin-1. A recent report identified a role for CARD9 in innate anti-fungal responses, demonstrating CARD9-Bcl10-mediated activation of NF-κB and pro-inflammatory cytokine induction in murine bone marrow-derived DC (bmDC) stimulated via Dectin-1. We now report that Dectin-1-CARD9 signals fail to activate NF-κB and drive TNF-α induction in murine bone marrow-derived macrophages (bmM). However, priming of bmM with GM-CSF or IFN-γ permits Dectin-1-CARD9-mediated TNF-α induction. Analysis of other macrophage/DC populations revealed further variation in the ability of Dectin-1-CARD9 signaling to drive TNF-α production. Resident peritoneal cells and alveolar macrophages produce TNF-α upon Dectin-1 ligation, while thioglycollate-elicited peritoneal macrophages and Flt3L-derived DC do not. We present data demonstrating that CARD9 is recruited to phagosomes via its CARD domain where it enhances TLR-induced cytokine production even in cells in which Dectin-1 is insufficient to drive cytokine production. In such cells, Dectin-1, CARD9 and Bcl10 levels are not limiting, and data indicate that these cells express additional factors that restrict Dectin-1-CARD9 signaling for TNF-α induction.
登录
查看更多内容
Dectin-1介导β-葡聚糖的生物学作用。
DOI：
10.1084/jem.20021890
发表时间：
2003-05-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Brown GD;Herre J;Williams DL;Willment JA;Marshall AS;Gordon S
通讯作者：
Gordon S
影响因子：
30.5
作者：
Gaide, O;Favier, B;Thome, M
通讯作者：
Thome, M
影响因子：
4.4
作者：
Meyer-Wentrup, Friederike;Figdor, Carl G.;van Spriel, Annemiek B.
通讯作者：
van Spriel, Annemiek B.
影响因子：
15.9
作者：
Dillon, S;Agrawal, S;Pulendran, B
通讯作者：
Pulendran, B
影响因子：
20.3
作者：
Underhill, DM;Rossnagle, E;Simmons, RM
通讯作者：
Simmons, RM