Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

CiteULike is a free service for managing and discovering scholarly references - click here to get started.

Sign In to gain access to subscriptions and/or personal tools.
Journal of Endotoxin Research
This Article
Right arrow Full Text (PDF)
Right arrow References
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Tapping, R. I.
Right arrow Articles by Tobias, P. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tapping, R. I.
Right arrow Articles by Tobias, P. S.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Mycobacterial lipoarabinomannan mediates physical interactions between TLR1 and TLR2 to induce signaling

Richard I. Tapping

Department of Microbiology, College of Medicine, University of Illinois, Urbana, Illinois, USA

Peter S. Tobias

Department of Immunology, The Scripps Research Institute, La Jolla, California, USA, tobias{at}scripps.edu

Mycobacteria and their cell wall component lipoarabinomannan (LAM) have recently been established as agonists for TLR2. Our transfection studies with single and pairwise combinations of TLRs 1, 2, 6 and 10 reveal that only TLR1 and TLR2 together mediate strong activation of NF-KB-driven luciferase activity in response to LAM. Co-operative signaling by TLR1 and TLR2 is observed using either non-capped or mannose-capped LAM as a stimulus. Moreover, we have found that phosphatidylinositol mannosides, simple biosynthetic precursors of LAM, also activate cells through the combined actions of TLR1 and TLR2. Co-immunoprecipitation studies show that TLR1 and TLR2 are physically associated, independently of the presence of LAM. To address the mechanism of LAM-induced TLR activation we have used TLR fusion proteins in a protein fragment complementation assay. The results of this assay suggest that LAM alters the physical interaction between the intracellular signaling domains of TLR1 and TLR2. Together, these results identify LAM as an agonist for TLR1 and TLR2 and support the idea that LAM initiates transmembrane signaling by altering the physical association between TLR1 and TLR2.

Journal of Endotoxin Research, Vol. 9, No. 4, 264-268 (2003)
DOI: 10.1177/09680519030090040801
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?