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Collaborative induction of inflammatory responses by dectin-1 and Toll-like receptor 2. J Exp Med 2003 May 05;197(9):1107-17

Date

04/30/2003

Pubmed ID

12719479

Pubmed Central ID

PMC2193968

DOI

10.1084/jem.20021787

Scopus ID

2-s2.0-0038558249   1198 Citations

Abstract

Toll-like receptors (TLRs) mediate recognition of a wide range of microbial products including lipopolysaccharides, lipoproteins, flagellin, and bacterial DNA, and signaling through TLRs leads to the production of inflammatory mediators. In addition to TLRs, many other surface receptors have been proposed to participate in innate immunity and microbial recognition, and signaling through some of these receptors is likely to cooperate with TLR signaling in defining inflammatory responses. In this report we have examined how dectin-1, a lectin family receptor for beta-glucans, collaborates with TLRs in recognizing microbes. Dectin-1, which is expressed at low levels on macrophages and high levels on dendritic cells, contains an immunoreceptor tyrosine-based activation motif-like signaling motif that is tyrosine phosphorylated upon activation. The receptor is recruited to phagosomes containing zymosan particles but not to phagosomes containing immunoglobulin G-opsonized particles. Dectin-1 expression enhances TLR-mediated activation of nuclear factor kappa B by beta-glucan-containing particles, and in macrophages and dendritic cells dectin-1 and TLRs are synergistic in mediating production of cytokines such as interleukin 12 and tumor necrosis factor alpha. Additionally, dectin-1 triggers production of reactive oxygen species, an inflammatory response that is primed by TLR activation. The data demonstrate that collaborative recognition of distinct microbial components by different classes of innate immune receptors is crucial in orchestrating inflammatory responses.

Author List

Gantner BN, Simmons RM, Canavera SJ, Akira S, Underhill DM

Author

Benjamin N. Gantner PhD Assistant Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

3T3 Cells
Animals
Base Sequence
Cytokines
DNA Primers
Enzyme Activation
Inflammation
Lectins, C-Type
Macrophages
Membrane Glycoproteins
Membrane Proteins
Mice
NADPH Oxidases
Nerve Tissue Proteins
Receptors, Cell Surface
Toll-Like Receptor 2
Toll-Like Receptors
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