Specific recognition of Candida albicans by macrophages requires galectin-3 to discriminate Saccharomyces cerevisiae and needs association with TLR2 for signaling
Specific recognition of Candida albicans by macrophages requires galectin-3 to discriminate Saccharomyces cerevisiae and needs association with TLR2 for signaling
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DOI：
10.4049/jimmunol.177.7.4679
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发表时间：
2006-10-01
影响因子：
4.4
通讯作者：
Poulain, Daniel
中科院分区：
文献类型：
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作者：
Jouault, Thierry;Behi, Miryam El Abed-El;Poulain, Daniel
巨噬细胞谱系细胞的刺激是免疫系统感知酵母的关键步骤。白色念珠菌和酿酒酵母细胞壁中存在的聚糖已被证明可作为不同受体的配体，导致不同的刺激途径，其中一些需要受体共同参与。然而，在这些配体-受体对中，没有一个被证明能区分致病性酵母C。白色念珠菌。我们探讨了半乳糖凝集素-3的作用，它结合C。白色念珠菌β-1，2甘露糖苷。这些聚糖在白色念珠菌表面特异性表达，但在S.啤酒。使用小鼠细胞系和来自敲除小鼠的半乳糖凝集素-3缺失细胞，我们证明了与S. cerevisiae，依赖于半乳糖凝集素-3的表达。然而，半乳糖凝集素-3是不需要的酵母菌的识别和内吞作用。相反，使用PMA诱导分化的THP-1，我们观察到TLR 2的存在是白色念珠菌和S.啤酒。TLR 2和半乳糖凝集素-3，这是在含有白色念珠菌的吞噬体的水平上表达的，显示出与该唯一物种孵育后在分化的巨噬细胞中相关。这些数据表明，巨噬细胞不同的感觉C。白色念珠菌和S.通过涉及TLR 2和半乳糖凝集素-3的机制，其可能与表达对白色念珠菌细胞壁表面特异性的β-1，2甘露糖苷的配体结合有关。
Stimulation of cells of the macrophage lineage is a crucial step in the sensing of yeasts by the immune system. Glycans present in both Candida albicans and Saccharomyces cerevisiae cell walls have been shown to act as ligands for different receptors leading to different stimulating pathways, some of which need receptor co-involvement. However, among these ligand-receptor couples, none has been shown to discriminate the pathogenic yeast C. albicans. We explored the role of galectin-3, which binds C. albicans beta-1,2 mannosides. These glycans are specifically and prominently expressed at the surface of C albicans but not on S. cerevisiae. Using a mouse cell line and galectin-3-deleted cells from knockout mice, we demonstrated a specific enhancement of the cellular response to C albicans compared with S. cerevisiae, which depended on galectin-3 expression. However, galectin-3 was not required for recognition and endocytosis of yeasts. In contrast, using PMA-induced differentiated THP-1, we observed that the presence of TLR2 was required for efficient uptake and endocytosis of both C albicans and S. cerevisiae. TLR2 and galectin-3, which are expressed at the level of phagosomes containing C albicans, were shown to be associated in differentiated macrophages after incubation with this sole species. These data suggest that macrophages differently sense C. albicans and S. cerevisiae through a mechanism involving TLR2 and galectin-3, which probably associate for binding of ligands expressing beta-1,2 mannosides specific to the C albicans cell wall surface.