Alum interaction with dendritic cell membrane lipids is essential for its adjuvanticity

被引：331

作者：

Flach, Tracy L. ^{[1
,2
]}

Ng, Gilbert ^{[1
,2
]}

Hari, Aswin ^{[1
,2
]}

Desrosiers, Melanie D. ^{[1
,2
]}

Zhang, Ping ^{[3
,4
]}

Ward, Sandra M. ^{[3
,4
]}

Seamone, Mark E. ^{[5
]}

Vilaysane, Akosua ^{[5
]}

Mucsi, Ashley D. ^{[1
,2
]}

Fong, Yin ^{[1
,2
]}

Prenner, Elmar ^{[6
]}

Ling, Chang Chun ^{[3
,4
]}

Tschopp, Jurg ^{[7
]}

Muruve, Daniel A. ^{[5
]}

Amrein, Matthias W. ^{[8
]}

Shi, Yan ^{[1
,2
]}

机构：

[1] Univ Calgary, Dept Microbiol & Infect Dis, Immunol Res Grp, Calgary, AB, Canada

[2] Univ Calgary, Snyder Inst, Calgary, AB, Canada

[3] Univ Calgary, Dept Chem, Calgary, AB T2N 1N4, Canada

[4] Univ Calgary, Alberta Ingenu Ctr Carbohydrate Sci, Calgary, AB, Canada

[5] Univ Calgary, Dept Med, Calgary, AB, Canada

[6] Univ Calgary, Dept Biol Sci, Calgary, AB T2N 1N4, Canada

[7] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland

[8] Univ Calgary, Dept Biol & Anat, Calgary, AB, Canada

来源：

NATURE MEDICINE | 2011年 / 17卷 / 04期

基金：

美国国家卫生研究院;

关键词：

MONOSODIUM URATE CRYSTALS; NALP3; INFLAMMASOME; NLRP3; CROSS-PRESENTATION; VACCINE ADJUVANTS; IMMUNE-RESPONSES; SOLID-SURFACES; URIC-ACID; ACTIVATION; PHAGOCYTOSIS;

D O I：

10.1038/nm.2306

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：479 / U121

页数：10

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