CD209 (DC-SIGN) signaling

Stable Identifier
R-HSA-5621575
Type
Pathway
Species
Homo sapiens
Related Species
Mycobacterium tuberculosis
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CD209 (also called as DC-SIGN (DC-specific intracellular adhesion molecule-3-grabbing non-integrin)) is a type II transmembrane C-type lectin receptor preferentially expressed on dendritic cells (DCs). CD209 functions as a pattern recognition receptor (PRR) that recognises several microorganisms and pathogens, contributing to generation of pathogen-tailored immune responses (Gringhuis & Geijtenbeek 2010, den Dunnen et al. 2009, Svajger et al. 2010). CD209 interacts with different mannose-expressing pathogens such as Mycobacterium tuberculosis and HIV-1 (Gringhuis et al. 2007, Geijtenbeek et al. 2000a). It also acts as an adhesion receptor that interacts with ICAM2 (intracellular adhesion molecule-2) on endothelial cells and ICAM3 on T cells (Geijtenbeek et al. 2000b,c). CD209 functions not only as an independent PRR, but is also implicated in the modulation of Toll-like receptor (TLR) signaling at the level of the transcription factor NF-kB (Gringhuis et al. 2009). CLEC7A (Dectin-1) and CD209 (DC-SIGN) signalling modulates Toll-like receptor (TLR) signalling through the kinase RAF1 that is independent of the SYK pathway but integrated with it at the level of NF-kB activation. The activation of RAF1 by CLEC7A or CD209 does not lead to activation of extracellular signal-regulated kinase 1 (ERK1)/2 or Mitogen-activated protein kinase kinase 1 (MEK1)/2 but leads to the phosphorylation and subsequent acetylation of RELA (p65). RELA phosphorylated on S276 not only positively regulates the activity of p65 through acetylation of p65, but also represses RELB activity by sequestering active RELB into inactive p65-RELB dimers that do not bind DNA (Gringhuis et al. 2007, Svajger et al. 2010, Jacque et al. 2005). RAF1-dependent signaling pathway is crucial in dectin-1 mediated immunity as it modulates both the canonical (promoting p65 phosphorylation and acetylation) and non-canonical (forming inactive p65-RELB dimers) NK-kB activation.

Literature References
PubMed ID Title Journal Year
18998127 Innate signaling by the C-type lectin DC-SIGN dictates immune responses

den Dunnen, J, Gringhuis, SI, Geijtenbeek, TB

Cancer Immunol. Immunother. 2009
20816209 Carbohydrate signaling by C-type lectin DC-SIGN affects NF-kappaB activity

Gringhuis, SI, Geijtenbeek, TB

Meth. Enzymol. 2010
17462920 C-type lectin DC-SIGN modulates Toll-like receptor signaling via Raf-1 kinase-dependent acetylation of transcription factor NF-kappaB

Gringhuis, SI, den Dunnen, J, Litjens, M, van Het Hof, B, van Kooyk, Y, Geijtenbeek, TB

Immunity 2007
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