Mannan-binding lectin inhibits Candida albicans-induced cellular responses in PMA-activated THP-1 cells through Toll-like receptor 2 and Toll-like receptor 4.
Mannan-binding lectin inhibits Candida albicans-induced cellular responses in PMA-activated THP-1 cells through Toll-like receptor 2 and Toll-like receptor 4.
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甘露聚糖结合凝集素通过 Toll 样受体 2 和 Toll 样受体 4 抑制 PMA 激活的 THP-1 细胞中白色念珠菌诱导的细胞反应
DOI：
10.1371/journal.pone.0083517
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Song S
中科院分区：
文献类型：
--
作者：
Wang M;Wang F;Yang J;Zhao D;Wang H;Shao F;Wang W;Sun R;Ling M;Zhai J;Song S
背景白色念珠菌（C.白色念珠菌），最常见的人类真菌病原体，在某些情况下可导致致命的全身感染。甘露聚糖结合凝集素（MBL）是C型凝集素超家族中凝集素家族的一员，是与先天免疫相关的重要血清成分。Toll样受体（TLR）广泛表达，并已被证明参与C。白色念珠菌诱导的细胞反应。我们首先研究了MBL是否调节热灭活（HK）C。白色念珠菌在佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）活化的人THP-1巨噬细胞中诱导的细胞应答。然后，我们研究了其抑制作用的可能机制。方法/主要发现酶联免疫吸附试验（ELISA）和逆转录聚合酶链反应（RT-PCR）分析表明，较高浓度（10-20 μg/ml）的MBL可显著减弱C.白色念珠菌诱导的趋化因子（例如，IL-8）和促炎细胞因子（例如，TNF-α）在蛋白质和mRNA水平从PMA激活的THP-1细胞产生。电泳迁移率变动分析（EMSA）和蛋白质印迹（WB）分析表明，MBL对C.白色念珠菌诱导PMA激活的THP-1细胞核因子-κB（NF-κB）DNA结合及其转位。MBL可直接与PMA激活的THP-1细胞结合，并可降低C.白色念珠菌诱导的THP-1巨噬细胞。抗TLR 2单克隆抗体（克隆TL2.1）和抗TLR 4单克隆抗体（克隆HTA 125）均能部分抑制这种结合。此外，免疫共沉淀实验和微量威尔斯滴定实验表明，MBL可直接与重组可溶性TLR 2胞外结构域（sTLR 2）和sTLR 4结合。结论MBL可通过修饰C.白念珠菌-/TLR-信号通路。本研究支持MBL在C.白色念珠菌诱导的细胞反应。
Background Candida albicans (C. albicans), the most common human fungal pathogen, can cause fatal systemic infections under certain circumstances. Mannan-binding lectin (MBL),a member of the collectin family in the C-type lectin superfamily, is an important serum component associated with innate immunity. Toll-like receptors (TLRs) are expressed extensively, and have been shown to be involved in C. albicans-induced cellular responses. We first examined whether MBL modulated heat-killed (HK) C. albicans-induced cellular responses in phorbol 12-myristate 13-acetate (PMA)-activated human THP-1 macrophages. We then investigated the possible mechanisms of its inhibitory effect. Methodology/Principal Finding Enzyme-linked immunosorbent assay (ELISA) and reverse transcriptasepolymerase chain reaction (RT-PCR) analysis showed that MBL at higher concentrations (10–20 µg/ml) significantly attenuated C. albicans-induced chemokine (e.g., IL-8) and proinflammatory cytokine (e.g., TNF-α) production from PMA-activated THP-1 cells at both protein and mRNA levels. Electrophoretic mobility shift assay (EMSA) and Western blot (WB) analysis showed that MBL could inhibit C. albicans-induced nuclear factor-κB (NF-κB) DNA binding and its translocation in PMA-activated THP-1 cells. MBL could directly bind to PMA-activated THP-1 cells in the presence of Ca2+, and this binding decreased TLR2 and TLR4 expressions in C. albicans-induced THP-1 macrophages. Furthermore, the binding could be partially inhibited by both anti-TLR2 monoclonal antibody (clone TL2.1) and anti-TLR4 monoclonal antibody (clone HTA125). In addition, co-immunoprecipitation experiments and microtiter wells assay showed that MBL could directly bind to the recombinant soluble form of extracellular TLR2 domain (sTLR2) and sTLR4. Conclusions/Significance Our study demonstrates that MBL can affect proinflammatory cytokine and chemokine expressions by modifying C. albicans-/TLR-signaling pathways. This study supports an important role for MBL on the regulation of C. albicans-induced cellular responses.
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甘露糖结合凝集素增强了吞噬体的Toll样受体2和6信号传导。
影响因子：
15.3
作者：
Ip, W. K. Eddie;Takahashi, Kazue;Moore, Kathryn J.;Stuart, Lynda M.;Ezekowitz, R. Alan B.
通讯作者：
Ezekowitz, R. Alan B.
影响因子：
5.5
作者：
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影响因子：
4.4
作者：
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通讯作者：
Romani, L
影响因子：
56.9
作者：
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通讯作者：
Hostetter, MK
影响因子：
4.8
作者：
Iwaki, D;Mitsuzawa, H;Kuroki, Y
通讯作者：
Kuroki, Y