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Nat Immunol. 2005 Jun;6(6):579-86. Epub 2005 May 15.

Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12.

Author information

  • 1Department of Microbiology and Immunology and the Cancer Research Institute, University of California San Francisco, San Francisco, California 94143, USA.

Erratum in

  • Nat Immunol. 2009 Feb;10(2):223. Dosage error in article text.

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.

PMID:
15895090
[PubMed - indexed for MEDLINE]
PMCID:
PMC1282462
Free PMC Article

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