Alum interaction with dendritic cell membrane lipids is essential for its adjuvanticity
Alum interaction with dendritic cell membrane lipids is essential for its adjuvanticity
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DOI：
10.1038/nm.2306
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发表时间：
2011-04-01
期刊：
影响因子：
82.9
通讯作者：
Shi, Yan
中科院分区：
文献类型：
--
作者：
Flach, Tracy L.;Ng, Gilbert;Shi, Yan
作为一种被批准用于人类的疫苗佐剂，明矾具有巨大的健康影响，但是，由于它是一种晶体，关于其机制的问题仍然存在。此外，对明矾参与的靶细胞、受体和信号通路知之甚少。在这里，我们报告说，独立的炎性小体和膜蛋白，明矾结合树突状细胞（DC）质膜脂质与实质性的力量。随后的脂质分选激活导致抗原摄取的失败的吞噬反应。这种活化的DC，在没有进一步与明矾结合的情况下，通过粘附分子细胞间粘附分子-1（ICAM-1）和淋巴细胞功能相关抗原-1（LFA-1）显示出与CD 4（+）T细胞的高亲和力和稳定结合。我们提出明矾通过改变膜脂质结构来触发DC反应。因此，这项研究提出了一个意想不到的机制，这种晶体结构如何与免疫系统相互作用，以及DC质膜如何作为固体结构的一般传感器。
As an approved vaccine adjuvant for use in humans, alum has vast health implications, but, as it is a crystal, questions remain regarding its mechanism. Furthermore, little is known about the target cells, receptors, and signaling pathways engaged by alum. Here we report that, independent of inflammasome and membrane proteins, alum binds dendritic cell (DC) plasma membrane lipids with substantial force. Subsequent lipid sorting activates an abortive phagocytic response that leads to antigen uptake. Such activated DCs, without further association with alum, show high affinity and stable binding with CD4(+) T cells via the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1). We propose that alum triggers DC responses by altering membrane lipid structures. This study therefore suggests an unexpected mechanism for how this crystalline structure interacts with the immune system and how the DC plasma membrane may behave as a general sensor for solid structures.