Affinage

CD209

CD209 antigen · UniProt Q9NNX6

Length
404 aa
Mass
45.8 kDa
Annotated
2026-04-28
100 papers in source corpus 35 papers cited in narrative 35 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD209/DC-SIGN is a C-type lectin receptor on dendritic cells that functions as a pattern-recognition receptor for mannose- and fucose-containing glycans on diverse pathogens and as an adhesion receptor mediating dendritic cell trafficking. Its carbohydrate recognition domain binds high-mannose N-glycans and Lewis x-type structures on pathogens including HIV-1 gp120, mycobacterial ManLAM, SARS-CoV-2 spike protein, and various viral glycoproteins, while its neck domain drives pH-sensitive tetramerization that enhances ligand avidity and enables pH-dependent ligand release after internalization into endosomal compartments (PMID:19502234, PMID:17055489, PMID:34341769). The cytoplasmic tail is required for receptor-mediated endocytosis and routing of captured cargo to distinct intracellular compartments—early endosomes for soluble antigens versus surface-accessible invaginated pockets for particulate antigens—with antigen size governing trafficking fate and functional outcomes including trans-infection of T cells by HIV-1 (PMID:11825572, PMID:31270240). DC-SIGN ligation activates intracellular signaling through LARG-mediated Rho-GTPase activation for viral synapse formation, Raf-1-dependent phosphorylation of NF-κB p65 at Ser276 to promote transcription elongation, and sphingomyelinase-driven ceramide generation that reorganizes receptor nanoclusters, collectively modulating TLR-dependent immune responses and pathogen exploitation of dendritic cells (PMID:17496896, PMID:20364151, PMID:21379338, PMID:12515809).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2000 High

    DC-SIGN was established as an adhesion receptor mediating dendritic cell trafficking, resolving the question of how DCs interact with endothelium under physiological shear flow.

    Evidence Shear flow adhesion and transmigration assays across endothelial monolayers using ICAM-2 as vascular ligand

    PMID:11017109

    Open questions at the time
    • Signaling downstream of ICAM-2 engagement not characterized
    • In vivo relevance in human DC migration not demonstrated
  2. 2002 High

    The cytoplasmic tail was shown to be required for DC-SIGN-mediated HIV internalization into a non-lysosomal compartment and for trans-infection of T cells, establishing the endocytic function as central to DC-SIGN's role in HIV pathogenesis.

    Evidence Cytoplasmic tail deletion mutants combined with HIV internalization and trans-infection assays; Nef-mediated inhibition of DC-SIGN endocytosis enhancing viral transmission

    PMID:11825572 PMID:11825573

    Open questions at the time
    • Identity of the non-lysosomal compartment not defined at molecular level
    • Cytoplasmic tail binding partners mediating endocytosis not identified
  3. 2003 High

    DC-SIGN was identified as the dominant receptor for M. tuberculosis entry into DCs via ManLAM binding, and ManLAM engagement was shown to suppress TLR-mediated DC maturation, revealing pathogen subversion of innate immunity through DC-SIGN.

    Evidence Antibody blocking with ManLAM binding studies and DC maturation assays across mycobacterial species

    PMID:12515809 PMID:12515819

    Open questions at the time
    • Signaling pathway from DC-SIGN to TLR suppression not molecularly defined
    • Later knockout studies showed ManLAM/PIM6 are not the sole mycobacterial DC-SIGN ligands (PMID:19651855)
  4. 2006 High

    Comprehensive glycan array screening defined DC-SIGN's dual specificity for mannose and fucose glycans, mapped its ligand repertoire to oligomannose N-glycans and Lewis x trisaccharides, and extended its pathogen recognition to E. coli LPS core and measles virus glycoproteins.

    Evidence Glycan array with >100 structures and quantitative binding; LPS core mutant panel for E. coli phagocytosis; MV attachment versus entry dissection in transfected cells

    PMID:16537615 PMID:16951363 PMID:17055489

    Open questions at the time
    • How dual mannose/fucose specificity is structurally accommodated in a single CRD binding site not fully resolved
    • Relative contribution of each glycan type to in vivo pathogen capture unknown
  5. 2007 High

    DC-SIGN was found to organize into nanoclusters on the DC surface and to signal through the Rho-GEF LARG upon HIV engagement, establishing that DC-SIGN is not merely an adhesion/capture receptor but actively transduces intracellular signals that promote viral synapse formation.

    Evidence Near-field scanning optical microscopy for nanocluster visualization; phosphoproteomics and gene expression profiling identifying LARG-Rho pathway and ATF3 upregulation

    PMID:17496896 PMID:17577901

    Open questions at the time
    • How cytoplasmic tail connects to LARG activation molecularly unclear
    • Whether LARG pathway is engaged by non-viral DC-SIGN ligands not tested
  6. 2008 High

    A Raf-1–NF-κB p65 Ser276 phosphorylation–pTEF-b axis was identified downstream of DC-SIGN/gp120 engagement, revealing how DC-SIGN signaling co-opts transcription elongation machinery to support HIV-1 replication in DCs.

    Evidence Signaling pathway dissection with kinase inhibitors, phosphorylation site mapping, and transcription elongation assays

    PMID:20364151

    Open questions at the time
    • Relationship between Raf-1 and LARG signaling arms not clarified
    • Whether Raf-1 pathway modulates immune gene transcription beyond viral genes not fully explored
  7. 2009 High

    Biophysical studies resolved DC-SIGN's quaternary structure as a pH-sensitive tetramer mediated by the neck domain, with an extended conformation on membranes that undergoes conformational change upon glycan binding, explaining avidity-based pathogen capture and pH-triggered ligand release in endosomes.

    Evidence SAXS-based molecular envelope and pH-dependent oligomerization; surface force measurements between lipid bilayers with neoglycolipid ligands

    PMID:19502234 PMID:19553201

    Open questions at the time
    • Full atomic-resolution structure of the intact tetramer not determined
    • How conformational change is transmitted to cytoplasmic signaling unknown
  8. 2010 Medium

    Live-cell imaging revealed directed lateral mobility of DC-SIGN clusters from the leading edge to medial lamellar endocytic sites, and DC-SIGN was shown to recognize apoptotic neutrophil Mac-1 and to be epigenetically regulated during DC differentiation, broadening its functional context beyond pathogen capture.

    Evidence Single-particle tracking and FRAP on immature DCs; antibody blocking of Mac-1–DC-SIGN interaction with DC maturation readout; bisulfite sequencing and histone ChIP during monocyte-to-DC differentiation

    PMID:18270264 PMID:20219612 PMID:20818162

    Open questions at the time
    • Motor or cytoskeletal mechanism driving directed DC-SIGN mobility not identified
    • Functional consequence of epigenetic regulation on pathogen handling not tested
  9. 2011 High

    DC-SIGN ligation was shown to activate sphingomyelinases generating ceramide that reorganizes receptor nanoclusters and recruits CD150 to enhance measles virus uptake, and the neck domain was confirmed as the determinant of superior HIV-1 capture through tetramerization.

    Evidence SMase activity assays with ceramide detection and CD150 co-clustering analysis; DC-SIGN/DCIR chimera and truncation constructs with HIV capture assays

    PMID:21379338 PMID:24928041

    Open questions at the time
    • Whether ceramide-mediated reorganization applies to all DC-SIGN ligands or is measles-specific
    • Direct structural basis of neck-domain tetramerization at atomic level lacking
  10. 2014 High

    Atomic-resolution structural studies by NMR and X-ray crystallography detailed the CRD binding mode for Lewis x and glycomimetic antagonists, revealing that a monovalent pseudomannotrioside can cluster DC-SIGN tetramers, providing a basis for therapeutic antagonist design.

    Evidence NMR (HSQC, STD, trNOE) of CRD–Lewis x; X-ray co-crystal structures with glycomimetics; ITC, AUC, and DLS demonstrating tetramer clustering

    PMID:24749535 PMID:25121780

    Open questions at the time
    • In vivo efficacy of glycomimetic antagonists not tested
    • Whether tetramer clustering by monovalent ligand occurs on intact cell membranes unknown
  11. 2018 Medium

    TLR4 co-stimulation was found to redirect DC-SIGN cargo to the cytosol for proteasome-dependent cross-presentation to CD8+ T cells, revealing cooperative innate receptor crosstalk that shapes adaptive immunity.

    Evidence Imaging flow cytometry with proteasome inhibitors and antigen-specific CD8+ T cell activation assays in human DCs

    PMID:29963041

    Open questions at the time
    • Molecular mechanism of cargo translocation from endosome to cytosol not identified
    • Whether this pathway operates for all DC-SIGN-captured antigens or only specific ligands unclear
  12. 2019 Medium

    Antigen particle size was demonstrated to determine DC-SIGN intracellular routing fate—soluble antigens to early endosomes versus particulate antigens to surface-accessible invaginated pockets—and a DC-SIGN–Lyn–PI3K signaling axis was identified in cancer cells, extending DC-SIGN function beyond immune contexts.

    Evidence Glycopolymers of defined size with endosomal marker colocalization; co-immunoprecipitation of DC-SIGN–Lyn–p85 complex with functional metastasis assays

    PMID:31217502 PMID:31270240

    Open questions at the time
    • Mechanism determining size-dependent sorting at the molecular level unknown
    • Lyn–PI3K pathway identified only in colorectal cancer cells, not confirmed in primary DCs
  13. 2021 High

    CD209 was identified as an alternative entry receptor for SARS-CoV-2 via spike RBD binding, relevant in tissues with low ACE2 expression, expanding the pandemic significance of DC-SIGN.

    Evidence Purified S-RBD binding assays, siRNA knockdown of CD209, and SARS-CoV-2 infection of endothelial cells

    PMID:34341769

    Open questions at the time
    • Glycan dependence of spike–DC-SIGN interaction not fully characterized
    • Relative contribution of DC-SIGN versus ACE2 in vivo across tissues not quantified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full atomic structure of the intact DC-SIGN tetramer with neck domain, the molecular mechanism coupling CRD ligand engagement to cytoplasmic signaling through LARG, Raf-1, and sphingomyelinase pathways, the identity of additional mycobacterial DC-SIGN ligands beyond ManLAM/PIM6, and the in vivo hierarchy of DC-SIGN among alternative pathogen receptors.
  • Full-length tetramer atomic structure unavailable
  • Cytoplasmic tail–signaling adaptor interactions not structurally resolved
  • In vivo mouse models limited by absence of true DC-SIGN ortholog

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 5 GO:0038024 cargo receptor activity 3 GO:0098631 cell adhesion mediator activity 2
Localization
GO:0005768 endosome 3 GO:0005886 plasma membrane 2 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-168256 Immune System 5 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 3 R-HSA-5653656 Vesicle-mediated transport 3
Partners
ARHGEF12ICAM2LYNPIK3R1RAF1SMPD1SMPD2
Complex memberships
DC-SIGN tetramer

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 DC-SIGN supports tethering and rolling of DC-SIGN-positive cells on the vascular ligand ICAM-2 under shear flow, and the DC-SIGN-ICAM-2 interaction regulates chemokine-induced transmigration of DCs across resting and activated endothelium, establishing DC-SIGN as central to DC trafficking. Shear flow adhesion assay, transmigration assay across endothelial monolayers Nature immunology High 11017109
2002 DC-SIGN mediates rapid internalization of intact HIV into a low-pH, non-lysosomal compartment; internalized virus retains infectivity; removal of the DC-SIGN cytoplasmic tail reduced viral uptake and abrogated trans-enhancement of T cell infection, establishing the cytoplasmic tail as required for endocytosis-dependent trans-infection. Cytoplasmic tail deletion mutants, HIV internalization assay, trans-infection T cell assay Immunity High 11825572
2002 HIV-1 Nef protein causes upregulation of DC-SIGN surface levels on HIV-1-infected DCs by inhibiting DC-SIGN endocytosis, which dramatically increases DC-T lymphocyte clustering and HIV-1 transmission. HIV-1 infection of DCs, Nef expression constructs, flow cytometry for DC-SIGN surface levels, clustering and transmission assays Immunity High 11825573
2003 DC-SIGN captures and internalizes intact Mycobacterium bovis BCG through the mycobacterial cell wall component ManLAM; ManLAM binding to DC-SIGN prevents mycobacteria- or LPS-induced DC maturation by interfering with TLR-mediated signals; blocking antibodies against DC-SIGN reverse this immunosuppressive effect. Antibody blocking assays, DC maturation assays (cytokine production, surface marker upregulation), ManLAM binding studies The Journal of experimental medicine High 12515809
2003 DC-SIGN is the major receptor for M. tuberculosis entry into human monocyte-derived DCs; the mycobacteria-specific lipoglycan LAM was identified as a key DC-SIGN ligand; complement receptor 3 and mannose receptor play a minor role in mycobacterial binding to DCs. Antibody blocking, receptor-specific inhibition, comparative receptor analysis on DCs and macrophages The Journal of experimental medicine High 12515819
2006 DC-SIGN specificity for mannose- and fucose-containing glycans was mapped using a large glycan array; DC-SIGN binds with Kd <2 µM to multivalent Lewis x (Galbeta1-4(Fucalpha1-3)GlcNAc) trisaccharides; selective binding observed to oligomannose-type N-glycans and LacdiNAc-fucose; no binding to core-fucose-linked N-glycans. Glycan array screening, binding affinity measurements FEBS letters High 17055489
2007 DC-SIGN activation by HIV or DC-SIGN-specific antibody induces signaling via the Rho guanine nucleotide-exchange factor LARG, leading to increased Rho-GTPase activity; this LARG activation is required for formation of virus-T cell synapses, while DC-SIGN engagement downregulates MHC class II and interferon-response genes and upregulates ATF3. Large-scale gene expression profiling, phosphoproteomic analysis of tyrosine-phosphorylated proteome, functional virus-T cell synapse assay Nature immunology High 17496896
2008 HIV-1 gp120 binding to DC-SIGN induces kinase Raf-1-dependent phosphorylation of NF-κB subunit p65 at Ser276, which recruits the transcription-elongation factor pTEF-b to nascent viral transcripts; pTEF-b-mediated phosphorylation of RNA polymerase II at Ser2 then enables transcription elongation and generation of full-length viral transcripts required for HIV-1 replication in DCs. Signaling pathway dissection, phosphorylation assays, inhibitor studies, transcription elongation assays Nature immunology High 20364151
2009 DC-SIGN's neck domain controls pH-sensitive oligomerization: the extracellular domain exists in equilibrium between monomeric and tetrameric states dependent on pH and ionic strength; SAXS-based molecular envelope demonstrates the neck domain is central to oligomerization, extended conformation, and carbohydrate recognition domain organization, implicating pH-driven dissociation in ligand release after internalization. Solution X-ray scattering (SAXS), hydrodynamic measurements, pH-dependent oligomerization assays The Journal of biological chemistry High 19502234
2009 Surface force measurements show DC-SIGN is in an extended conformation on membranes; glycan binding is associated with a conformational change that repositions the carbohydrate-recognition domains; lateral mobility of membrane-bound ligands enhances engagement of multiple CRDs in the receptor oligomer with appropriately spaced ligands. Surface force measurements between apposed lipid bilayers, neoglycolipid binding studies Proceedings of the National Academy of Sciences of the United States of America High 19553201
2011 DC-SIGN ligation on DCs by antibodies, mannan, or measles virus causes rapid activation of neutral and acid sphingomyelinases (SMase), leading to ceramide accumulation in the outer membrane leaflet; SMase activation promotes DC-SIGN signaling and recruits CD150 from intracellular LAMP-1+ compartments to the surface where it co-clusters with DC-SIGN, enhancing measles virus uptake. SMase activity assays, ceramide detection, co-clustering analysis, confocal microscopy of CD150 trafficking PLoS pathogens High 21379338
2011 DC-SIGN acts as a receptor for phleboviruses (Rift Valley fever and Uukuniemi viruses) by binding viral glycoproteins via high-mannose N-glycans; DC-SIGN is required for both viral attachment and endocytosis; an endocytosis-defective DC-SIGN mutant cannot mediate virus uptake; internalized virus separates from DC-SIGN and traffics to late endosomes. DC-SIGN endocytosis-defective mutants, live-cell virus-receptor clustering visualization, viral infection assays Cell host & microbe High 21767814
2006 DC-SIGN serves as a novel attachment receptor for both laboratory-adapted and wild-type measles virus strains via the MV glycoproteins F and H; DC-SIGN does not support MV entry (no susceptibility in DC-SIGN-transfected CHO cells) but is required for efficient MV infection of immature DCs in cis by enhancing CD46/CD150-mediated infection. DC-SIGN transfection in CHO cells, antibody blocking, attachment and infection assays Journal of virology High 16537615
2008 Human herpesvirus 8 (HHV-8) uses DC-SIGN as an entry receptor in B cells; DC-SIGN-mediated endocytosis is required for HHV-8 infection, as DC-SIGN lacking the transmembrane domain (unable to mediate endocytosis) cannot support infection; HHV-8 infection of B cells increases DC-SIGN expression and decreases CD20 and MHC class I. DC-SIGN truncation mutants, endocytic pathway inhibitors, HHV-8 infection assays (viral DNA, lytic/latency protein expression, infectious virus production) Journal of virology High 18337571
2008 DC-SIGN binds HHV-8 glycoprotein B (gB) in a dose-dependent manner via high-mannose carbohydrate structures on gB; key amino acids in the DC-SIGN carbohydrate recognition domain are required for HHV-8 infection. Biochemical binding assay (gB-DC-SIGN interaction), site-directed mutagenesis of DC-SIGN CRD, infection assays Virus research Medium 25018023
2006 DC-SIGN mediates binding and phagocytosis of E. coli through interactions with the complete core region of LPS (outer core); pathogenic E. coli strains expressing O-antigen, which masks core LPS, are not phagocytosed via DC-SIGN. LPS core mutants of E. coli, phagocytosis assays in DC-SIGN-expressing cells Journal of immunology High 16951363
2009 Hexamannosylated PIM6 (containing terminal alpha(1→2)-linked mannosyl residues identical to ManLAM caps) is a high-affinity DC-SIGN ligand; however, a PIM6-deficient BCG mutant and a PIM6/ManLAM double knockout bound DC-SIGN similarly to wild-type, indicating other unknown mycobacterial ligands dominate the DC-SIGN interaction. Synthetic and natural PIM binding assays, M. bovis BCG knockout strains (ΔpimE, ΔpimE ΔcapA), DC binding assays, cytokine measurement Infection and immunity High 19651855
2010 DC-SIGN clusters on the plasma membrane of immature DCs are preferentially localized to the leading edge of the lamellipod and undergo directed lateral mobility at high velocity (~1420 nm/s) from the leading edge to medial lamellar sites where endocytosis occurs, suggesting a mechanism for pathogen capture followed by internalization. Live-cell fluorescence microscopy, single-particle tracking, FRAP, colocalization with endocytic markers Journal of cell science Medium 18270264
2007 DC-SIGN receptors are organized in nanosized domains (clusters) on the dendritic cell plasma membrane, with ~80% of receptors in nanoclusters; heterogeneous molecular packing density within clusters was revealed by near-field scanning optical microscopy with single-molecule resolution. Near-field scanning optical microscopy (NSOM), single-molecule detection, sequential photobleaching Chemphyschem Medium 17577901
2006 CD4 coexpression with DC-SIGN impairs HIV-1 transmission to T cells: CD4 promotes internalization and intracellular retention of HIV-1 into late endosomal compartments (CD63+/CD81+), and Nef-mediated CD4 downregulation on MDDCs correlates with enhanced viral transmission. DC-SIGN-CD4 co-expression in Raji cells, HIV-1 internalization assays, confocal microscopy, late endosome markers Journal of virology Medium 17151103
2014 NMR structural characterization of DC-SIGN CRD interaction with Lewis X (Le^X) trisaccharide reveals significant chemical shift perturbations identifying residues near the binding site; STD and trNOE NMR experiments defined binding epitopes and bound conformations of Le^X distinct from those in previous crystal structures. 2D NMR (HSQC), STD-NMR, transferred NOE NMR, molecular modeling Biochemistry High 25121780
2014 Crystal structures of the DC-SIGN carbohydrate recognition domain complexed with glycomimetic antagonists (pseudomannobioside and pseudomannotrioside) reveal identical binding modes despite different inhibitory potencies; compound 2 (pseudomannotrioside) clusters DC-SIGN tetramers without multivalent scaffold, as determined by ITC, analytical ultracentrifugation, and DLS. X-ray crystallography, isothermal titration calorimetry (ITC), analytical ultracentrifugation, dynamic light scattering, SPR competition ACS chemical biology High 24749535
2019 Antigen particle size determines DC-SIGN-mediated intracellular routing: soluble glycopolymers are directed to transferrin-labeled early endosomes, while particulate antigens (aggregated polymers) are diverted to surface-accessible invaginated pockets that also harbor HIV-1, indicating antigen structure controls DC-SIGN trafficking fate. Ring-opening metathesis polymerization of glycopolymers, confocal microscopy, colocalization with endosomal markers Proceedings of the National Academy of Sciences of the United States of America High 31270240
2011 Semen clusterin, but not serum clusterin, binds DC-SIGN with high affinity (Kd 76 nM) through fucose-containing blood-type antigens (Le^x and Le^y) expressed on its glycans, and can abrogate HIV-1 binding to DC-SIGN. Affinity binding assays, blocking of HIV-1 capture, glycan structural analysis (Le^x/Le^y identification) Journal of immunology Medium 22013110
2015 MUC1 is identified as the major milk glycoprotein that binds to the lectin domain of DC-SIGN in human milk, via Lewis x-type oligosaccharides, and prevents pathogen interaction with DC-SIGN; this effect is specific to human milk and not present in formula, bovine, or camel milk. Affinity binding assays, glycan inhibition, comparative milk analysis Frontiers in immunology Medium 25821450
2015 LECT2 (leukocyte cell-derived chemotaxin 2) signals through CD209/DC-SIGN receptor to phosphorylate JNK in human endothelial cells and macrophages, inducing ICAM-1, TNFα, MCP-1, and IL-1β expression; CD209 siRNA knockdown abolishes LECT2-induced JNK phosphorylation and downstream inflammatory responses. siRNA knockdown of CD209, Western blot for JNK phosphorylation, qPCR for inflammatory mediators, JNK inhibitor studies Metabolism: clinical and experimental Medium 26123523
2008 DC-SIGN acts as a receptor for avian H5N1 influenza virus; DC-SIGN-expressing cells (B-THP-1/DC-SIGN and T-THP-1/DC-SIGN) capture and transfer H5N1 pseudotyped and reverse-genetics virus particles to target cells (cis and trans infection); anti-DC-SIGN monoclonal antibodies block this transfer. Capture and transfer assays, DC-SIGN-expressing cell lines, antibody blocking, electron microscopy Biochemical and biophysical research communications Medium 18593570
2010 DC-SIGN-mediated uptake of M. tuberculosis-induced apoptotic neutrophils activates dendritic cells; inhibitory studies showed that DC contact-dependent DC activation requires binding of PMN Mac-1 (CD11b/CD18) to DC-SIGN, with endocytic activity involving αvβ5 but not scavenger receptor CD36. Antibody blocking assays for DC-SIGN, Mac-1, αvβ5, CD36; DC maturation readouts after apoptotic PMN-DC contact Human immunology Medium 20219612
2010 IL-4 increases CD209 expression on human Schwann cells, leading to increased binding and uptake of M. leprae; CD209-positive Schwann cells show higher M. leprae binding than CD209-negative Schwann cells; Th1 cytokines do not induce CD209 on Schwann cells. CD209 expression analysis in primary Schwann cells and cell lines, M. leprae binding assays, cytokine treatment (IL-4 vs. Th1 cytokines) Infection and immunity Medium 20713631
2021 CD209/DC-SIGN interacts with the SARS-CoV-2 spike receptor-binding domain (S-RBD) and can mediate SARS-CoV-2 entry into human cells; CD209 knockdown inhibits virus entry; CD209 functions as an alternative SARS-CoV-2 receptor relevant in tissues with low ACE2 expression. Biochemical binding assays with purified recombinant S-RBD, siRNA knockdown, SARS-CoV-2 infection assays in endothelial cells ACS central science High 34341769
2019 DC-SIGN physically interacts with Lyn kinase; DC-SIGN activation recruits Lyn and p85 to form a DC-SIGN-Lyn-p85 complex that promotes PI3K/Akt/β-catenin signaling in colorectal cancer cells, increasing transcription of MMP-9 and VEGF and promoting TCF1/LEF1-mediated suppression of miR-185. Co-immunoprecipitation, Western blot, knockdown/overexpression experiments, in vitro and in vivo metastasis assays Cell death and differentiation Medium 31217502
2017 DC-SIGN functions as more than just an attachment factor for dengue virus; using internalization-deficient DC-SIGN mutants (alanine substitutions in 3 cytoplasmic internalization motifs, or cytoplasmic truncation), DC-SIGN co-localizes with DENV inside cells and all 3 DC-SIGN molecules still support cell infection, implying involvement of a co-receptor for internalization-deficient forms. Internalization-deficient DC-SIGN mutants, confocal and super-resolution imaging, single-particle tracking, infectivity assays Traffic (Copenhagen, Denmark) Medium 28128492
2018 TLR4 triggering simultaneously with DC-SIGN causes translocation of DC-SIGN cargo to the cytosol in human DCs, leading to proteasome-dependent processing and increased CD8+ T cell activation (cross-presentation), revealing a TLR4-DC-SIGN cooperation pathway for cytosolic antigen routing. Imaging flow cytometry, antigen-specific CD8+ T cell activation assays, proteasome inhibitors, TLR4 ligand co-stimulation Frontiers in immunology Medium 29963041
2011 The DC-SIGN neck domain, but not the CRD, confers higher binding affinity to HIV gp120 via formation of tetramers; chimera and truncate analysis of DC-SIGN and DCIR demonstrates DC-SIGN's superior HIV-1 capture and transfer capability is neck-domain dependent. Soluble DC-SIGN/DCIR truncation and chimeric constructs, HIV capture and transfer assays Virology Medium 24928041
2010 During DC-SIGN expression upregulation at the CD209 locus upon monocyte-to-DC differentiation, two CpG dinucleotides (CpG2 and CpG3) in the CD209 promoter show marked demethylation, and 'active' histone modifications are acquired while 'repressive' marks are lost, establishing an epigenetic mechanism for CD209 gene activation. Bisulfite sequencing, ChIP for histone modifications, gene expression analysis during differentiation Epigenetics Medium 20818162

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Mycobacteria target DC-SIGN to suppress dendritic cell function. The Journal of experimental medicine 797 12515809
2003 DC-SIGN is the major Mycobacterium tuberculosis receptor on human dendritic cells. The Journal of experimental medicine 464 12515819
2002 DC-SIGN-mediated internalization of HIV is required for trans-enhancement of T cell infection. Immunity 403 11825572
2000 DC-SIGN-ICAM-2 interaction mediates dendritic cell trafficking. Nature immunology 395 11017109
2003 Unique appearance of proliferating antigen-presenting cells expressing DC-SIGN (CD209) in the decidua of early human pregnancy. The American journal of pathology 230 12598322
2005 A variant in the CD209 promoter is associated with severity of dengue disease. Nature genetics 229 15838506
2006 Specificity of DC-SIGN for mannose- and fucose-containing glycans. FEBS letters 228 17055489
2010 HIV-1 exploits innate signaling by TLR8 and DC-SIGN for productive infection of dendritic cells. Nature immunology 217 20364151
2021 CD209L/L-SIGN and CD209/DC-SIGN Act as Receptors for SARS-CoV-2. ACS central science 212 34341769
2010 C-type lectin DC-SIGN: an adhesion, signalling and antigen-uptake molecule that guides dendritic cells in immunity. Cellular signalling 192 20363321
2011 DC-SIGN as a receptor for phleboviruses. Cell host & microbe 190 21767814
2001 Five mouse homologues of the human dendritic cell C-type lectin, DC-SIGN. International immunology 160 11581173
2002 HIV-1 Nef-induced upregulation of DC-SIGN in dendritic cells promotes lymphocyte clustering and viral spread. Immunity 157 11825573
2007 Activation of the lectin DC-SIGN induces an immature dendritic cell phenotype triggering Rho-GTPase activity required for HIV-1 replication. Nature immunology 156 17496896
2013 The physiological role of DC-SIGN: a tale of mice and men. Trends in immunology 147 23608151
2003 DC-SIGN: a novel HIV receptor on DCs that mediates HIV-1 transmission. Current topics in microbiology and immunology 142 12797442
2008 Innate signaling by the C-type lectin DC-SIGN dictates immune responses. Cancer immunology, immunotherapy : CII 124 18998127
2004 Functional comparison of the mouse DC-SIGN, SIGNR1, SIGNR3 and Langerin, C-type lectins. International immunology 124 15096474
2006 DC-SIGN and immunoregulation. Cellular & molecular immunology 118 16978536
2002 DC-SIGN, a C-type lectin on dendritic cells that unveils many aspects of dendritic cell biology. Journal of leukocyte biology 118 12050176
2001 Placental expression of DC-SIGN may mediate intrauterine vertical transmission of HIV. The Journal of pathology 115 11745695
2012 Dectin-1 and DC-SIGN polymorphisms associated with invasive pulmonary Aspergillosis infection. PloS one 114 22384201
2006 Measles virus targets DC-SIGN to enhance dendritic cell infection. Journal of virology 114 16537615
2008 Human herpesvirus 8 infects and replicates in primary cultures of activated B lymphocytes through DC-SIGN. Journal of virology 107 18337571
2009 DC-SIGN neck domain is a pH-sensor controlling oligomerization: SAXS and hydrodynamic studies of extracellular domain. The Journal of biological chemistry 102 19502234
2007 Non-carbohydrate inhibitors of the lectin DC-SIGN. Journal of the American Chemical Society 95 17902657
2012 Glycan-based DC-SIGN targeting vaccines to enhance antigen cross-presentation. Molecular immunology 92 23158834
2021 CD209L/L-SIGN and CD209/DC-SIGN act as receptors for SARS-CoV-2. bioRxiv : the preprint server for biology 90 32607506
2005 Binding and transfer of human immunodeficiency virus by DC-SIGN+ cells in human rectal mucosa. Journal of virology 89 15827191
2014 A multivalent inhibitor of the DC-SIGN dependent uptake of HIV-1 and Dengue virus. Biomaterials 86 24508075
2008 CD209 genetic polymorphism and tuberculosis disease. PloS one 85 18167547
2011 DC-SIGN mediated sphingomyelinase-activation and ceramide generation is essential for enhancement of viral uptake in dendritic cells. PLoS pathogens 82 21379338
2007 The DC-SIGN-related lectin LSECtin mediates antigen capture and pathogen binding by human myeloid cells. Blood 81 17339424
2009 Pathogen recognition by DC-SIGN shapes adaptive immunity. Future microbiology 78 19722841
2020 Blockade of DC-SIGN+ Tumor-Associated Macrophages Reactivates Antitumor Immunity and Improves Immunotherapy in Muscle-Invasive Bladder Cancer. Cancer research 73 32060149
2016 Human DC-SIGN binds specific human milk glycans. The Biochemical journal 71 26976925
2009 Role of phosphatidylinositol mannosides in the interaction between mycobacteria and DC-SIGN. Infection and immunity 69 19651855
2006 Role of N-acetylglucosamine within core lipopolysaccharide of several species of gram-negative bacteria in targeting the DC-SIGN (CD209). Journal of immunology (Baltimore, Md. : 1950) 69 16951363
2008 Decreased pathology and prolonged survival of human DC-SIGN transgenic mice during mycobacterial infection. Journal of immunology (Baltimore, Md. : 1950) 67 18453604
2003 A fatal attraction: Mycobacterium tuberculosis and HIV-1 target DC-SIGN to escape immune surveillance. Trends in molecular medicine 67 12727141
2008 DC-SIGN mediates avian H5N1 influenza virus infection in cis and in trans. Biochemical and biophysical research communications 65 18593570
2020 C-type Lectin CD209L/L-SIGN and CD209/DC-SIGN: Cell Adhesion Molecules Turned to Pathogen Recognition Receptors. Biology 63 33375175
2011 Semen clusterin is a novel DC-SIGN ligand. Journal of immunology (Baltimore, Md. : 1950) 61 22013110
2007 Nanoscale organization of the pathogen receptor DC-SIGN mapped by single-molecule high-resolution fluorescence microscopy. Chemphyschem : a European journal of chemical physics and physical chemistry 61 17577901
2015 Cross-presentation through langerin and DC-SIGN targeting requires different formulations of glycan-modified antigens. Journal of controlled release : official journal of the Controlled Release Society 60 25656175
2008 DC-sign+ CD163+ macrophages expressing hyaluronan receptor LYVE-1 are located within chorion villi of the placenta. Placenta 59 18078989
2013 DC-SIGN, DC-SIGNR and LSECtin: C-type lectins for infection. International reviews of immunology 56 24156700
2011 Quinoxalinone Inhibitors of the Lectin DC-SIGN. Chemical science 56 22639721
2009 Binding-site geometry and flexibility in DC-SIGN demonstrated with surface force measurements. Proceedings of the National Academy of Sciences of the United States of America 56 19553201
2005 The core lipopolysaccharide of Escherichia coli is a ligand for the dendritic-cell-specific intercellular adhesion molecule nonintegrin CD209 receptor. Journal of bacteriology 53 15716442
2015 LECT2 induces atherosclerotic inflammatory reaction via CD209 receptor-mediated JNK phosphorylation in human endothelial cells. Metabolism: clinical and experimental 52 26123523
2006 CD4 coexpression regulates DC-SIGN-mediated transmission of human immunodeficiency virus type 1. Journal of virology 51 17151103
2008 Distribution and lateral mobility of DC-SIGN on immature dendritic cells--implications for pathogen uptake. Journal of cell science 49 18270264
2014 Structural characterization of the DC-SIGN-Lewis(X) complex. Biochemistry 48 25121780
2008 Human dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin (CD209) is a receptor for Yersinia pestis that promotes phagocytosis by dendritic cells. Infection and immunity 48 18285492
2008 Synthesis of novel DC-SIGN ligands with an alpha-fucosylamide anchor. Chembiochem : a European journal of chemical biology 48 18655085
2019 Antigen structure affects cellular routing through DC-SIGN. Proceedings of the National Academy of Sciences of the United States of America 47 31270240
2010 High numbers of DC-SIGN+ dendritic cells in lesional skin of cutaneous T-cell lymphoma. Journal of the American Academy of Dermatology 47 20466174
2008 Utilization of DC-SIGN for entry of feline coronaviruses into host cells. Journal of virology 47 18799586
2005 DC-SIGN mediates the binding of Aspergillus fumigatus and keratinophylic fungi by human dendritic cells. Immunobiology 47 16164024
2017 Beyond attachment: Roles of DC-SIGN in dengue virus infection. Traffic (Copenhagen, Denmark) 44 28128492
2010 Identification of four novel DC-SIGN ligands on Mycobacterium bovis BCG. Protein & cell 43 21203928
2013 Antigen-presenting cell candidates for HIV-1 transmission in human distal colonic mucosa defined by CD207 dendritic cells and CD209 macrophages. AIDS research and human retroviruses 41 24134315
2019 DC-SIGN-LEF1/TCF1-miR-185 feedback loop promotes colorectal cancer invasion and metastasis. Cell death and differentiation 40 31217502
2018 Mouse DC-SIGN/CD209a as Target for Antigen Delivery and Adaptive Immunity. Frontiers in immunology 40 29867967
2008 Dermal-type macrophages expressing CD209/DC-SIGN show inherent resistance to dengue virus growth. PLoS neglected tropical diseases 40 18827881
2019 Molecular Insights into DC-SIGN Binding to Self-Antigens: The Interaction with the Blood Group A/B Antigens. ACS chemical biology 39 31283166
2015 Human Milk Blocks DC-SIGN-Pathogen Interaction via MUC1. Frontiers in immunology 39 25821450
2014 Unique DC-SIGN clustering activity of a small glycomimetic: A lesson for ligand design. ACS chemical biology 39 24749535
2017 Identification of Multiple Druggable Secondary Sites by Fragment Screening against DC-SIGN. Angewandte Chemie (International ed. in English) 38 28523851
2011 Epigenotype switching at the CD14 and CD209 genes during differentiation of human monocytes to dendritic cells. Epigenetics 38 20818162
2022 CD209/CD14+ Dendritic Cells Characterization in Rheumatoid and Psoriatic Arthritis Patients: Activation, Synovial Infiltration, and Therapeutic Targeting. Frontiers in immunology 37 35095831
2016 Phenotype and Function of CD209+ Bovine Blood Dendritic Cells, Monocyte-Derived-Dendritic Cells and Monocyte-Derived Macrophages. PloS one 35 27764236
2018 Toll-Like Receptor 4 Triggering Promotes Cytosolic Routing of DC-SIGN-Targeted Antigens for Presentation on MHC Class I. Frontiers in immunology 33 29963041
2013 In vivo targeting of human DC-SIGN drastically enhances CD8⁺ T-cell-mediated protective immunity. European journal of immunology 33 23784881
2006 Analysis of DC-SIGN (CD209) functional variants in patients with tuberculosis. Human immunology 33 17055357
2019 Unraveling Sugar Binding Modes to DC-SIGN by Employing Fluorinated Carbohydrates. Molecules (Basel, Switzerland) 32 31242623
2008 CD209 gene polymorphisms in South Indian HIV and HIV-TB patients. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 32 19126442
2016 Pseudo-Mannosylated DC-SIGN Ligands as Immunomodulants. Scientific reports 31 27734954
2014 Human herpesvirus 8 glycoprotein B binds the entry receptor DC-SIGN. Virus research 31 25018023
2010 Targeting DC-SIGN with carbohydrate multivalent systems. Drug news & perspectives 30 21152451
2015 Dendritic cells respond to nasopharygeal carcinoma cells through annexin A2-recognizing DC-SIGN. Oncotarget 29 25402728
2007 Lewis X oligosaccharides targeting to DC-SIGN enhanced antigen-specific immune response. Immunology 29 17371544
2002 Capture and transfer of simian immunodeficiency virus by macaque dendritic cells is enhanced by DC-SIGN. Journal of virology 28 12414925
2016 PPAR-γ agonist pioglitazone regulates dendritic cells immunogenicity mediated by DC-SIGN via the MAPK and NF-κB pathways. International immunopharmacology 26 27792919
2014 DC-SIGN plays a stronger role than DCIR in mediating HIV-1 capture and transfer. Virology 26 24928041
2010 Dendritic cell activation by sensing Mycobacterium tuberculosis-induced apoptotic neutrophils via DC-SIGN. Human immunology 25 20219612
2006 DC-SIGN association with the Th2 environment of lepromatous lesions: cause or effect? The Journal of pathology 25 16583355
2021 A Remote Secondary Binding Pocket Promotes Heteromultivalent Targeting of DC-SIGN. Journal of the American Chemical Society 24 34748320
2017 Tongue Sole CD209: A Pattern-Recognition Receptor that Binds a Broad Range of Microbes and Promotes Phagocytosis. International journal of molecular sciences 24 28869534
2012 BODIPY-labeled DC-SIGN-targeting glycodendrons efficiently internalize and route to lysosomes in human dendritic cells. Biomacromolecules 24 22920925
2010 Design, synthesis and activity evaluation of mannose-based DC-SIGN antagonists. Molecular diversity 24 21076980
2020 Lipopolysaccharide-induced DC-SIGN/TLR4 crosstalk activates NLRP3 inflammasomes via MyD88-independent signaling in gastric epithelial cells. Experimental cell research 23 32961144
2010 Interleukin-4 regulates the expression of CD209 and subsequent uptake of Mycobacterium leprae by Schwann cells in human leprosy. Infection and immunity 23 20713631
2018 Genetically-encoded fragment-based discovery of glycopeptide ligands for DC-SIGN. Bioorganic & medicinal chemistry 22 30344001
2014 Monovalent mannose-based DC-SIGN antagonists: targeting the hydrophobic groove of the receptor. European journal of medicinal chemistry 22 24556146
2011 Association of CD209 polymorphisms with tuberculosis in an Indonesian population. Human immunology 22 21704100
2006 Towards a crucial role for DC-SIGN in tuberculosis and beyond. Trends in microbiology 21 16876999
2018 Yersinia pseudotuberculosis Exploits CD209 Receptors for Promoting Host Dissemination and Infection. Infection and immunity 20 30348825
2003 Sugar and spice: viral envelope-DC-SIGN interactions in HIV pathogenesis. Current HIV research 20 15043214