Format

Send to

Choose Destination
Nat Med. 2011 Apr;17(4):479-87. doi: 10.1038/nm.2306. Epub 2011 Mar 13.

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

Author information

1
Immunology Research Group, Department of Microbiology & Infectious Diseases, and Snyder Institute, University of Calgary, Calgary, Alberta, Canada.

Abstract

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.

PMID:
21399646
DOI:
10.1038/nm.2306
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for Faculty of 1000
Loading ...
Support Center