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- Title
Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12.
- Authors
Hamerman, Jessica A; Tchao, Nadia K; Lowell, Clifford A; Lanier, Lewis L
- Abstract
DAP12 is a signaling adaptor containing an immunoreceptor tyrosine-based activation motif (ITAM) that pairs with receptors on myeloid cells and natural killer cells. We examine here the responses of mice lacking DAP12 to stimulation through Toll-like receptors (TLRs). Unexpectedly, DAP12-deficient macrophages produced higher concentrations of inflammatory cytokines in response to a variety of pathogenic stimuli. Additionally, macrophages deficient in spleen tyrosine kinase (Syk), which signals downstream of DAP12, showed a phenotype identical to that of DAP12-deficient macrophages. DAP12-deficient mice were more susceptible to endotoxic shock and had enhanced resistance to infection by the intracellular bacterium Listeria monocytogenes. These data suggest that one or more DAP12-pairing receptors negatively regulate signaling through TLRs.
- Publication
Nature immunology, 2005, Vol 6, Issue 6, p579
- ISSN
1529-2908
- Publication type
Journal Article
- DOI
10.1038/ni1204