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Journal of Cell Science 115, 2603-2611 (2002)
© 2002 The Company of Biologists Limited

Research Article

Mediators of innate immune recognition of bacteria concentrate in lipid rafts and facilitate lipopolysaccharide-induced cell activation

Martha Triantafilou1, Kensuke Miyake2, Douglas T. Golenbock3,* and Kathy Triantafilou1,{ddagger}

1 University of Portsmouth, School of Biological Sciences, King Henry Building, King Henry I Street, Portsmouth, PO1 2DY, UK
2 Department of Immunology, Saga Medical School, Nabeshima, Japan
3 Boston University School of Medicine, Boston Medical Center, The Maxwell Finland Laboratory for Infectious Diseases, Boston, Massachusetts 02118, USA
* Present address: Department of Medicine, Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, MA 01665, USA

{ddagger} Author for correspondence (e-mail: ktrian{at}hotmail.com )

Accepted 19 March 2002

The plasma membrane of cells is composed of lateral heterogeneities, patches and microdomains. These membrane microdomains or lipid rafts are enriched in glycosphingolipids and cholesterol and have been implicated in cellular processes such as membrane sorting and signal transduction. In this study we investigated the importance of lipid raft formation in the innate immune recognition of bacteria using biochemical and fluorescence imaging techniques. We found that receptor molecules that are implicated in lipopolysaccharide (LPS)-cellular activation, such as CD14, heat shock protein (hsp) 70, 90, Chemokine receptor 4 (CXCR4), growth differentiation factor 5 (GDF5) and Toll-like receptor 4 (TLR4), are present in microdomains following LPS stimulation. Lipid raft integrity is essential for LPS-cellular activation, since raft-disrupting drugs, such as nystatin or MCD, inhibit LPS-induced TNF-{alpha} secretion. Our results suggest that the entire bacterial recognition system is based around the ligation of CD14 by bacterial components and the recruitment of multiple signalling molecules, such as hsp70, hsp90, CXCR4, GDF5 and TLR4, at the site of CD14-LPS ligation, within the lipid rafts.

Key words: Lipid rafts, LPS, Heat shock proteins, CXCR4, GDF5, TLR4


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Lipid rafts in innate immunity

JCS 2002 115: 1202. [Full Text]  



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