Efficient capture of C. albicans and zymosan by SIGNR1 facilitates TLR2-dependent TNF-α production by macrophages
Efficient capture of C. albicans and zymosan by SIGNR1 facilitates TLR2-dependent TNF-α production by macrophages
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SIGNR1 有效捕获白色念珠菌和酵母聚糖促进巨噬细胞产生 TLR2 依赖性 TNF-α
DOI：
10.1093/intimm/dxr103
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
K.
中科院分区：
文献类型：
--
作者：
Takahara;K.
SIGNR1是一种小鼠c型凝集素，可以结合多种病原体，包括白色念珠菌。在本研究中，我们探讨了SIGNR1在c识别中的影响。使用转染了signr1的RAW264.7 （RAW-SIGNR1）细胞和常驻的腹膜巨噬细胞，抑制白色念珠菌/酶生蛋白和随后的肿瘤坏死因子(TNF)-α的产生。与raw -对照细胞相比，RAW-SIGNR1细胞在热杀伤dc刺激下显著增加TNF-α的产生。albicansand酵母聚糖。SIGNR1的微碳水化合物识别结构域（CRD）的识别对于增强TNF-α的产生至关重要。与此一致的是，抗signr1单抗显著降低了这种增强。拮抗Dectin-1配体Laminarin共同作用，进一步减弱反应，但在RAW-SIGNR1细胞中未观察到其自身的作用。然而，它适度地降低了raw控制细胞的反应。缺乏toll样受体（TLR）配体的Zymosan降低了应答，即使它被SIGNR1和Dectin-1识别。此外，拮抗tlr2消除了这种反应，表明TNF-α的产生主要依赖于tlr2介导的信号传导。表达SIGNR1的常驻腹膜巨噬细胞主要捕获腹腔注射的zymosan并产生TNF-α， TNF-α依赖于TLR2，部分被抗SIGNR1单抗抑制。最后，利用多种缺失突变体的免疫沉淀，通过CRD证实了SIGNR1与TLR2细胞外部分的物理关联。这些结果表明，识别微生物的SIGNR1与TLR2合作参与了Mφ增强TNF-α产生的过程。
SIGNR1, a mouse C-type lectin, binds various pathogens, includingCandida albicans. In this study, we explore the impact of SIGNR1 in the recognition ofC. albicans/zymosan and the subsequent tumor necrosis factor (TNF)-α production using SIGNR1-transfected RAW264.7 (RAW-SIGNR1) cells and resident peritoneal macrophages. Compared with RAW-control cells, RAW-SIGNR1 cells dramatically enhanced TNF-α production upon the stimulation with heat-killedC. albicansand zymosan. Recognition of microbesviacarbohydrate recognition domain (CRD) of SIGNR1 was crucial for the enhanced TNF-α production. Consistently, such an enhancement was significantly decreased by anti-SIGNR1 mAb. Laminarin, antagonistic Dectin-1 ligand, cooperated to further diminish the response, although no effect was observed by itself in RAW-SIGNR1 cells. However, it moderately reduced the response of RAW-control cells. Zymosan depleted of toll-like receptor (TLR) ligands decreased the response, even though it was recognized by SIGNR1 and Dectin-1. Moreover, antagonistic anti-TLR2 abolished the response, suggesting that TNF-α production largely relies on TLR2-mediated signaling. Resident peritoneal macrophages expressing SIGNR1 predominantly captured zymosan injected intra-peritoneally and produced TNF-α, which was dependent on TLR2 and partly inhibited by anti-SIGNR1 mAb. Finally, physical association of SIGNR1 with the extracellular portion of TLR2 through CRD was confirmed by immunoprecipitation using various deletion mutants. These results suggest that SIGNR1 recognizing microbes participates in the enhanced TNF-α production by Mφ in cooperation with TLR2.