Email updates

Keep up to date with the latest news and content from Arthritis Research & Therapy and BioMed Central.

This article is part of the supplement: Global Arthritis Research Network (GARN): 4th World Congress on Arthritis in Montreal

Oral presentation

The nonsense allele oblivious reveals a sensor of di-acylglycerides acting in conjunction with TLR2 and TLR6

K Hoebe1, K Tabeta1, P Georgel1, X Du1, S Mudd1, S Sovath1, L Shamel1, T Hartung2, Ul Zähringer3 and B Beutler1

Author Affiliations

1 The Scripps Research Institute, La Jolla, California, USA

2 Department of Biochemical Pharmacology, University of Konstanz, Konstanz, Germany

3 Research Center Borstel, Leipniz-center for Medicine and Bioscience, Borstel, Germany

For all author emails, please log on.

Arthritis Res Ther 2004, 6(Suppl 3):13  doi:10.1186/ar1347

The electronic version of this article is the complete one and can be found online at:


Published:13 September 2004

©

Oral presentation

The mammalian Toll-like receptors (TLRs) activate cells of the innate immune system when stimulated by diverse ligands of microbial origin. In some instances, these ligands are directly engaged by the TLRs; however, this is not necessarily true in all cases. TLR2 recognizes multiple, structurally disparate microbial ligands, consistent with a requirement for co-receptors in ligand binding. Using N-ethyl-N-nitrosourea, we generated the recessive immunodeficiency phenotype oblivious, in which macrophages show diminished awareness of the S-enantiomer of the di-acylated bacterial lipopeptide MALP-2 and lipoteichoic acid, together with spontaneous ocular colonization by Gram-positive organisms and hypersusceptibility to Staphylococcus aureus infection. Oblivious macrophages readily detect the tri-acylated bacterial lipopeptide PAM3CSK4 as well as zymosan, revealing that some TLR2 ligands are activated via an Oblivious-independent pathway. The gene responsible for the oblivious phenotype has been positionally cloned. In its ability to carry the lipoteichoic acid and MALP-2 signal to the transmembrane signaling receptors TLR2 and TLR6, Oblivious serves a function analogous to CD14, which concentrates the lipopolysacchardide signal for transduction by TLR4. Besides microbial molecules, oblivious also serves as a receptor for endogenous molecules and may mediate (some) of the inflammatory events involved in the development of atherosclerosis.