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Cited by 431

The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.

The CD14 Ligands Lipoarabinomannan and Lipopolysaccharide Differ in Their Requirement for Toll-Like Receptors

Means, Terry K, Lien, Egil, Yoshimura, Atsutoshi, Wang, Shuyan, Golenbock, Douglas T, Fenton, Matthew J·1999·The Journal of Immunology
DOI 10.4049/jimmunol.163.12.6748
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Abstract

Mammalian Toll-like receptor (TLR) proteins are new members of the IL-1 receptor family that participate in activation of cells by bacteria and bacterial products. Several recent reports indicate that TLR proteins mediate cellular activation by bacterial LPS via a signaling pathway that is largely shared by the type I IL-1 receptor. We previously showed that Chinese hamster ovary (CHO) fibroblasts engineered to express CD14 (CHO/CD14) were responsive to LPS, but not to a distinct CD14 ligand, mycobacterial lipoarabinomannan (LAM). These CHO/CD14 cells were subsequently found to possess a frame-shift mutation within the TLR2 gene which resulted in their inability to express functional TLR2 protein. Thus, we hypothesized that TLR2, but not TLR4, was necessary for LAM signaling. In this paper we show that CHO/CD14 cells engineered to express functional TLR2 protein acquired the ability to be activated by LAM. Similarly, overexpression of TLR2 in murine macrophages conferred enhanced LAM responsiveness. Together, our data demonstrate that the distinct CD14 ligands LAM and LPS utilize different TLR proteins to initiate intracellular signals. These findings suggest a novel receptor signaling paradigm in which the binding of distinct ligands is mediated by a common receptor chain, but cellular activation is initiated via distinct signal-transducing chains that confer ligand specificity. This paradigm contrasts with many cytokine receptor complexes in which receptor specificity is conferred by a unique ligand-binding chain but cellular activation is initiated via shared signal-transducing chains.

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Metadata

Authors
Means, T. K., Lien, E., Yoshimura, A., Wang, S., Golenbock, D. T., & Fenton, M. J.
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
1999-12
Volume
163
Issue
12
Pages
6748-6755
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.163.12.6748
OpenAlex
W2142602618
Cited by
431
References
3
FWCI
12.82
Type
journal article
Language
en
Open access
closed

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