Cutting edge: critical role of intracellular osteopontin in antifungal innate immune responses.
Cutting edge: critical role of intracellular osteopontin in antifungal innate immune responses.
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DOI：
10.4049/jimmunol.1002735
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发表时间：
2011-01-01
期刊：
影响因子：
--
通讯作者：
Shinohara ML
中科院分区：
文献类型：
--
作者：
Inoue M;Moriwaki Y;Arikawa T;Chen YH;Oh YJ;Oliver T;Shinohara ML
我们发现，在缺乏T和B细胞的免疫功能低下的Rag 2 −/−小鼠中，骨桥蛋白（OPN）的缺乏使小鼠对机会性真菌肺孢子虫非常敏感，尽管免疫活性OPN缺陷小鼠可以像野生型小鼠一样清除肺孢子虫。骨桥蛋白是一种细胞外蛋白，其在细胞内的作用尚不清楚。在这里，我们阐明了iOPN参与抗真菌先天免疫的机制。首先，iOPN对于检测肺孢子虫的真菌受体的簇形成至关重要;包括dectin-1，TLR 2和甘露糖受体。第二，iOPN在TLR 2和dectin-1信号通路中发挥衔接分子的作用，并通过酵母聚糖介导ERK激活和细胞因子产生，酵母聚糖同时激活TLR 2和dectin-1通路。第三，iOPN增强肺孢子虫的吞噬和清除。我们的研究表明iOPN在抗真菌先天免疫中的关键参与。
We found that absence of osteopontin (OPN) in immunocompromised Rag2−/− mice, which lack T and B cells, made the mice extremely susceptible to an opportunistic fungus Pneumocystis, although immunocompetent OPN-deficient mice could clear Pneumocystis as well as wild-type mice. OPN has been studied as an extracellular protein, and the role of an intracellular isoform of osteopontin (iOPN) is still largely unknown. Here, we elucidated the mechanism by which iOPN was involved in anti-fungal innate immunity. First, iOPN was essential for cluster formation of fungal receptors that detect Pneumocystis; including dectin-1, TLR2, and mannose receptor. Second, iOPN played a role as an adaptor molecule in TLR2 and dectin-1 signaling pathways, and mediated ERK activation and cytokine production by zymosan, which simultaneously activates TLR2 and dectin-1 pathways. Third, iOPN enhanced phagocytosis and clearance of Pneumocystis. Our study here suggests the critical involvement of iOPN in anti-fungal innate immunity.
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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：
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影响因子：
32.4
作者：
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影响因子：
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作者：
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影响因子：
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