Affinage

Showing CD209 — DC-SIGN is a alias.

CD209

CD209 antigen · UniProt Q9NNX6

Length
404 aa
Mass
45.8 kDa
Annotated
2026-06-09
100 papers in source corpus 39 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD209 (DC-SIGN) is a calcium-dependent C-type lectin that operates as a multivalent pattern-recognition and adhesion receptor on dendritic cells and macrophages, recognizing mannose- and fucose-terminated glycans to capture pathogens and shape adaptive immunity (PMID:10721995, PMID:12515809, PMID:31242623). Its carbohydrate-recognition domain coordinates a Ca2+ ion to engage mannose (via axial OH-2/equatorial OH-3) and fucose with highest affinity among monosaccharides, and accommodates Lewis X glycans in a binding mode distinct from mannose-terminated ligands (PMID:31242623, PMID:25121780); high-avidity ligand engagement depends on neck-domain tetramerization, which confers strong binding to HIV-1 gp120, while neck glycosylation and natural neck variants tune oligomerization and sugar binding (PMID:24928041, PMID:18073208). Through this glycan-recognition machinery DC-SIGN binds an exceptionally broad range of pathogens — HIV-1 gp120, mycobacterial ManLAM and hexamannosylated PIM6, dengue virus, Ebola and measles glycoproteins, HCV E2, HHV-8 gB, phlebovirus glycoproteins, and the SARS-CoV-2 spike RBD — as well as host ligands ICAM-2 and fucosylated milk glycans/MUC1 (PMID:10721995, PMID:12515809, PMID:19651855, PMID:12682107, PMID:16537615, PMID:12634366, PMID:25018023, PMID:21767814, PMID:34341769, PMID:11017109, PMID:25821450). Functionally it acts in three modes: as an adhesion molecule supporting DC tethering and rolling on endothelial ICAM-2 under shear flow (PMID:11017109); as an attachment/trans-infection factor that captures virus (HIV-1, HCV, measles) for delivery to susceptible target cells or, for phleboviruses, as an authentic endocytic entry receptor (PMID:10721995, PMID:15371595, PMID:16537615, PMID:21767814); and as an endocytic antigen receptor whose cytoplasmic internalization motifs route ligand to late endosomes/lysosomes for MHC-II presentation, with particulate versus soluble antigen physical properties dictating intracellular routing and a fraction directed to proteasome-dependent MHC-I cross-presentation (PMID:11859097, PMID:31270240, PMID:14576049). DC-SIGN is also a signaling receptor: ligation activates Raf-1 leading to NF-κB p65 acetylation that modulates TLR-induced cytokine output, and it couples to Lyn/Syk, PLCγ, ERK/Akt and calcium flux from lipid-raft-associated complexes (PMID:18998127, PMID:16434485). In vivo, coordinate DC-SIGN and TLR4 engagement by fucosylated ligands drives immunoregulatory IL-10 and transplantation tolerance (PMID:26070485), while DC-SIGN nanoscale clusters polarized to the lamellipod and a conformational change upon glycan docking provide the spatial and biophysical basis for multivalent capture and endocytosis (PMID:18270264, PMID:19553201). DC-SIGN expression is induced by IL-4 with GM-CSF and repressed by IFNs and TGF-β (PMID:11884427).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2000 High

    Established DC-SIGN's founding function as a pathogen-capture receptor that promotes infection of bystander cells rather than its own host cell, defining the trans-infection paradigm.

    Evidence Co-binding and trans-infection assays of HIV-1 gp120 in primary DCs and transfectants

    PMID:10721995

    Open questions at the time
    • Molecular basis of high-avidity gp120 binding not yet resolved
    • Did not address endocytic routing of captured virus
  2. 2000 High

    Showed DC-SIGN is also an adhesion receptor for endothelial ICAM-2, explaining how DC-SIGN+ cells tether, roll, and transmigrate, linking the lectin to leukocyte trafficking.

    Evidence Shear-flow chamber assays with antibody blocking in transfectants and primary DCs

    PMID:11017109

    Open questions at the time
    • Glycan determinant on ICAM-2 not mapped here
    • Relationship between adhesion and pathogen-binding sites unresolved
  3. 2000 Medium

    Mapped the CD209/CD209L locus and predicted the tandem-repeat neck and mannose-binding lectin domain architecture from sequence, providing the structural framework for later function.

    Evidence Genomic mapping, sequence analysis, tissue expression studies

    PMID:10975799

    Open questions at the time
    • Coiled-coil and lectin predictions not yet tested by mutagenesis
    • Functional consequences of neck repeats unestablished
  4. 2002 High

    Defined DC-SIGN as an endocytic antigen receptor by showing cytoplasmic internalization motifs drive ligand uptake to late endosomes/lysosomes and feed MHC-II antigen presentation.

    Evidence Cytoplasmic tail mutagenesis, fluorescence/EM imaging, CD4+ T cell presentation assays

    PMID:11859097

    Open questions at the time
    • Adaptors recognizing the internalization motif not identified
    • Determinants of routing beyond the motif unexamined
  5. 2003 High

    Identified DC-SIGN as the major dendritic-cell receptor for mycobacteria through ManLAM/LAM, and showed ligation subverts TLR-driven DC maturation, establishing an immune-evasion role.

    Evidence Antibody blocking, purified ManLAM/LAM binding, DC maturation and infection assays

    PMID:12515809 PMID:12515819

    Open questions at the time
    • Signaling pathway linking ManLAM to maturation block not yet defined
    • Other mycobacterial ligands not excluded
  6. 2003 Medium

    Broadened the ligand repertoire to demonstrate DC-SIGN serves as receptor or attachment factor for diverse pathogens (dengue, Ebola, HCV, Candida, Leishmania) and routes some cargo for MHC-I cross-presentation.

    Evidence Transfection gain-of-function, antibody blocking, pseudotype and binding assays, proteasome-inhibition/CTL assays across multiple pathogens

    PMID:12504546 PMID:12634366 PMID:12645952 PMID:12682107 PMID:14576049 PMID:14707095

    Open questions at the time
    • Which pathogens use DC-SIGN for productive entry versus attachment-only varies and is not uniformly resolved
    • Distinct endocytic compartments for different cargo not fully characterized
  7. 2006 High

    Demonstrated DC-SIGN is a bona fide signaling receptor coupling to Lyn/Syk, PLCγ, ERK/Akt and calcium flux from lipid rafts to modulate cytokine responses.

    Evidence Antibody cross-linking, phosphorylation and calcium assays, raft fractionation, Co-IP with Lyn/Syk, cytokine ELISA

    PMID:16434485

    Open questions at the time
    • Direct kinase–DC-SIGN interaction stoichiometry not defined
    • Link between proximal kinases and transcriptional output incomplete
  8. 2006 Medium

    Extended pathogen recognition to HHV-8, measles, Neisseria and platelet-mediated HIV capture, showing ligand-driven outcomes range from infection enhancement to receptor downregulation and immune suppression.

    Evidence Transfectant infection, soluble receptor/mannan blocking, glycan-mutant bacteria, platelet capture/infectivity assays

    PMID:16424204 PMID:16461738 PMID:16537615 PMID:16940507

    Open questions at the time
    • Mechanism of HHV-8-induced DC-SIGN downregulation not defined
    • In vivo relevance of platelet capture untested
  9. 2008 Medium

    Defined Raf-1 as a central node downstream of pathogen-triggered DC-SIGN, with NF-κB p65 acetylation as the effector that tunes TLR-induced gene programs.

    Evidence Kinase and p65 acetylation assays, gene-transcription profiling synthesized across pathogen studies

    PMID:18998127

    Open questions at the time
    • How distinct ligands selectively engage Raf-1 versus other pathways unclear
    • Connection between proximal Lyn/Syk and Raf-1 not bridged
  10. 2009 High

    Resolved the spatial and biophysical mechanics of multivalent capture: nanoscale clusters polarized to the lamellipod, directed lateral mobility to endocytic zones, and a glycan-docking conformational change repositioning the CRDs.

    Evidence Single-particle tracking live-cell imaging and surface-force measurements on DC-SIGN ectodomain/glycan bilayers

    PMID:18270264 PMID:19553201

    Open questions at the time
    • Cytoskeletal machinery driving directed cluster transport not identified
    • Conformational change not visualized at atomic resolution
  11. 2009 High

    Dissected mycobacterial PIM ligands, showing hexamannosylated PIM6 is a high-affinity ligand but is dispensable for whole-bacterium binding, indicating redundant ligands.

    Evidence Synthetic/natural PIM binding and pimE-mutant BCG binding to DC-SIGN and DCs

    PMID:19651855

    Open questions at the time
    • Dominant ligand on intact mycobacteria remains unidentified
  12. 2014 High

    Provided atomic-level glycan recognition detail, defining distinct Lewis X versus mannose binding modes and confirming the neck domain drives high-affinity gp120 binding via tetramerization.

    Evidence HSQC/STD/trNOE NMR with docking; domain-swap chimeras with HIV capture/transfer assays

    PMID:24928041 PMID:25121780

    Open questions at the time
    • Functional consequence of distinct binding modes for antigen routing untested
    • Neck contribution to non-HIV ligands not generalized
  13. 2015 High

    Established an immunoregulatory, tolerogenic role in vivo where fucose-driven DC-SIGN signaling cooperates with TLR4 to produce IL-10 and sustain transplantation tolerance, and a pathological role in follicular lymphoma BCR triggering.

    Evidence In vivo macrophage deletion and signaling interference with allograft/IL-10 readouts; FL B-cell BCR aggregation and kinase activation assays

    PMID:26070485 PMID:26272216

    Open questions at the time
    • Signaling branch distinguishing tolerogenic IL-10 from inflammatory output not fully mapped
    • FL findings from single lab and microenvironment-dependent
  14. 2019 High

    Showed antigen physical properties dictate intracellular routing — soluble glycopolymers to early endosomes, particulates to surface-accessible pockets shared with HIV-1 — explaining differential degradation versus retention.

    Evidence Defined synthetic glycopolymer series with quantitative confocal colocalization and trafficking

    PMID:31270240

    Open questions at the time
    • Molecular sorting machinery distinguishing the routes unknown
    • Consequences for presentation efficiency not quantified
  15. 2019 Medium

    Refined the carbohydrate-recognition chemistry, defining mannose Ca2+ coordination via axial OH-2/equatorial OH-3 and the fucose>mannose affinity hierarchy.

    Evidence 19F- and 1H-STD-NMR with molecular dynamics on purified CRD

    PMID:31242623

    Open questions at the time
    • Single-lab in vitro CRD studies; cellular relevance of binding hierarchy not tested
  16. 2021 High

    Identified non-canonical activities: a SARS-CoV-2 spike-RBD entry-receptor role in ACE2-low endothelial cells, a druggable allosteric secondary pocket enhancing glycan recognition, and a Lyn/p85-dependent pro-metastatic signaling axis in colorectal cancer.

    Evidence S-RBD binding/siRNA/soluble-CD209 entry assays; NMR/MD with heteromultivalent liposome targeting; Co-IP and PI3K/Akt/β-catenin pathway and metastasis assays

    PMID:31217502 PMID:34341769 PMID:34748320

    Open questions at the time
    • Physiological contribution of CD209 to SARS-CoV-2 infection in vivo unclear
    • Cancer signaling role from single lab in non-immune context

Open questions

Synthesis pass · forward-looking unresolved questions
  • How distinct ligands and antigen physical states selectively bias DC-SIGN between adhesion, trans-infection, endocytic presentation, and the Raf-1/NF-κB versus Lyn/Syk signaling outputs remains unresolved.
  • No unified model connecting ligand identity to signaling versus trafficking decisions
  • Adaptors linking cytoplasmic tail motifs to specific routes unidentified
  • In vivo physiological ligand spectrum incompletely defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0001618 virus receptor activity 3 GO:0038024 cargo receptor activity 3 GO:0060089 molecular transducer activity 3 GO:0008289 lipid binding 2 GO:0098631 cell adhesion mediator activity 1
Localization
GO:0005764 lysosome 2 GO:0005768 endosome 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-168256 Immune System 3 R-HSA-5653656 Vesicle-mediated transport 3
Partners
ICAM2LECT2LYNMUC1PIK3R1RAF1SYK

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 DC-SIGN (CD209) binds HIV-1 envelope glycoprotein gp120 on dendritic cells and promotes efficient trans-infection of CD4+/chemokine receptor-expressing T cells without mediating viral entry into DCs themselves. Co-binding assays, trans-infection assays, antibody blocking experiments in primary DCs and transfected cell lines Cell High 10721995
2000 DC-SIGN binds ICAM-2 on vascular endothelium and supports tethering and rolling of DC-SIGN-positive cells under shear flow, regulating chemokine-induced transmigration of dendritic cells across endothelium. Flow chamber assays under shear stress, antibody blocking, transfected cell lines expressing DC-SIGN Nature immunology High 11017109
2000 DC-SIGN and DC-SIGNR genes are located on chromosome 19p13 adjacent to CD23, share a similar genomic organization, and both encode proteins with tandem-repeat neck regions predicted to form coiled coils and mannose-binding C-type lectin domains. Genomic mapping, sequence analysis, expression studies in endometrium, placenta, and KG1 cells Journal of immunology Medium 10975799
2002 DC-SIGN is rapidly internalized upon soluble ligand binding via internalization motifs in its cytoplasmic tail; mutating a putative internalization motif reduces ligand-induced internalization. DC-SIGN-ligand complexes traffic to late endosomes/lysosomes, and ligands internalized by DC-SIGN are efficiently processed and presented to CD4+ T cells. Cytoplasmic tail mutagenesis, ratio fluorescence imaging, electron microscopy, antigen presentation assays to CD4+ T cells Journal of immunology High 11859097
2003 DC-SIGN captures and internalizes intact Mycobacterium bovis BCG through binding to the mycobacterial cell wall component ManLAM (mannose-capped lipoarabinomannan); anti-DC-SIGN antibodies block this infection. ManLAM binding to DC-SIGN prevents mycobacteria- or LPS-induced DC maturation, interfering with TLR-mediated signaling. Anti-DC-SIGN antibody blocking, DC infection assays, DC maturation assays (LPS stimulation), purified ManLAM binding experiments The Journal of experimental medicine High 12515809
2003 DC-SIGN is the major M. tuberculosis receptor on human dendritic cells; mycobacterial lipoarabinomannan (LAM) was identified as a key ligand. Complement receptor 3 and mannose receptor played minor roles in mycobacterial binding to DCs. Anti-DC-SIGN antibody blocking, binding assays with purified LAM, comparison with CR3/MR-blocking antibodies in human monocyte-derived DCs The Journal of experimental medicine High 12515819
2003 DC-SIGN (CD209) mediates productive dengue virus infection of human dendritic cells; all four dengue serotypes use DC-SIGN to infect DCs. Transfection of DC-SIGN into THP-1 cells confers dengue susceptibility; anti-DC-SIGN antibodies block DC infection. DC-SIGN transfection into THP-1 cells, anti-DC-SIGN antibody blocking, dengue infection assays The Journal of experimental medicine High 12682107
2003 DC-SIGN binds Ebola glycoproteins and greatly enhances transduction of primary cells (macrophages, dendritic cells) and endothelial cells by Ebola virus pseudotypes; DC-SIGN and DC-SIGNR do not directly mediate Ebola virus entry but act as attachment/enhancement factors. Ebola pseudotype transduction assays, primary cell infections, antibody blocking, transfected cell lines Virology Medium 12504546
2003 DC-SIGN is an antigen-uptake receptor for Candida albicans on dendritic cells; DC-SIGN internalizes C. albicans into DC-SIGN-enriched vesicles that are distinct from mannose receptor-containing vesicles, indicating separate endocytic routing. Binding assays in DC-SIGN transfectants and primary DCs, fluorescence microscopy showing DC-SIGN-enriched vesicles, comparison with mannose receptor compartments European journal of immunology Medium 12645952
2003 Hepatitis C virus E2 glycoprotein and E1/E2 pseudotypes bind DC-SIGN and DC-SIGNR expressed on cell lines and primary human endothelial cells; binding to immature MDDCs is dependent on DC-SIGN interactions. Binding assays with soluble E2 glycoprotein and HCV pseudotypes on DC-SIGN/DC-SIGNR transfectants and primary MDDCs; antibody-blocking experiments Journal of virology Medium 12634366
2003 DC-SIGN expression on B-cell lines dramatically enhances HIV-1 internalization; most captured virions are rapidly degraded in a lysosomal compartment, but a fraction is processed by the proteasome leading to MHC-I-restricted antigen presentation and activation of HIV-specific CTLs. DC-SIGN transfection into B-cell lines, HIV internalization assays, proteasome inhibitor experiments, CTL activation assays Blood Medium 14576049
2004 DC-SIGN-captured HCV pseudoviruses are internalized and trans-infect adjacent human liver cells; virus capture and transinfection require internalization of the SIGN-HCV pseudovirus complex. HCV pseudovirus transinfection assays, L-SIGN/DC-SIGN+ cell lines, internalization-dependent trans-infection assay Proceedings of the National Academy of Sciences Medium 15371595
2004 DC-SIGN discriminates among Leishmania species and life cycle forms; it is a receptor for promastigote and amastigote stages of L. infantum and L. pifanoi but not for L. major metacyclic promastigotes. Leishmania binding to DC-SIGN is independent of lipophosphoglycan. Binding assays with different Leishmania species/stages on DC-SIGN-expressing cells; LPG-deficient parasite binding experiments Journal of immunology Medium 14707095
2006 DC-SIGN engagement by specific antibodies induces ERK1/2 and Akt phosphorylation (without p38MAPK activation), PLCgamma phosphorylation, and transient intracellular calcium increases in DCs. A fraction of DC-SIGN partitions in lipid raft-enriched fractions and co-precipitates with tyrosine kinases Lyn and Syk. DC-SIGN cross-linking synergizes with TNF-α for IL-10 release and enhances LPS-induced IL-10. Antibody cross-linking, phosphorylation assays (ERK1/2, Akt, p38, PLCgamma), calcium flux assays, lipid raft fractionation, co-immunoprecipitation with Lyn and Syk, cytokine ELISA Blood High 16434485
2006 DC-SIGN is a receptor for Human Herpesvirus 8 (HHV-8) on myeloid DCs and macrophages; HHV-8 binding and infection are blocked by anti-DC-SIGN mAb, soluble DC-SIGN, and mannan. HHV-8 infection via DC-SIGN leads to down-regulation of DC-SIGN itself, decreased endocytic activity, and inhibition of CD8+ T cell antigen stimulation. Anti-DC-SIGN antibody and soluble DC-SIGN blocking, mannan competition, DC-SIGN transfected cell line infection assays, T cell stimulation assays Journal of immunology Medium 16424204
2006 DC-SIGN and CLEC-2 both contribute to HIV-1 capture by platelets; platelets express low levels of DC-SIGN and DC-SIGN-dependent capture of HIV-1 maintains virus in an infectious state over several days. Flow cytometry for DC-SIGN on platelets, antibody blocking with DC-SIGN and CLEC-2 inhibitors, HIV-1 infectivity assays Journal of virology Medium 16940507
2006 DC-SIGN mediates recognition and phagocytosis of Neisseria gonorrhoeae by dendritic cells only for a specific lipooligosaccharide (LOS) mutant (lgtB); wild-type GC avoids DC-SIGN recognition through LOS variation. DC-SIGN-mediated phagocytosis is blocked by anti-DC-SIGN antibody. HeLa-DC-SIGN transfectants, GC lgtB mutant binding and phagocytosis assays, anti-DC-SIGN antibody blocking Journal of leukocyte biology Medium 16461738
2006 Measles virus glycoproteins F and H are both DC-SIGN ligands; DC-SIGN does not support MV entry (does not confer susceptibility in CHO cells) but functions as an attachment receptor enhancing CD46/CD150-mediated infection of immature DCs in cis. DC-SIGN transfection in CHO cells (entry assay), DC-SIGN inhibitor blocking of DC infection, MV glycoprotein binding experiments Journal of virology Medium 16537615
2007 DC-SIGN neck region variants and the lectin domain both contribute to multimerization on the cell surface; glycosylation of the neck region negatively affects oligomer formation. Naturally occurring DC-SIGN neck variants differ in multimerization competence, exhibit altered sugar binding ability, but retain pathogen-interacting capacity. Structural analysis of neck variants, multimerization assays in transfected cells, sugar-binding assays, pathogen interaction assays with neck variant-expressing cells The Journal of biological chemistry Medium 18073208
2008 DC-SIGN triggering by pathogens activates a signaling pathway with a central role for the serine/threonine kinase Raf-1; Raf-1 activation leads to acetylation of NF-κB subunit p65, which induces specific gene transcription profiles and modulates TLR-induced cytokine responses. Kinase activation assays, NF-κB p65 acetylation assays, gene transcription profiling; described as established across multiple pathogen studies Cancer immunology, immunotherapy Medium 18998127
2009 DC-SIGN hexamannosylated PIM6 (containing terminal α(1→2)-linked mannosyl residues identical to the ManLAM mannose cap) binds DC-SIGN with high affinity, whereas di- and tetramannosylated PIMs (PIM2 and PIM4) do not. However, a pimE deletion mutant M. bovis BCG lacking PIM6 binds DC-SIGN similarly to wild type, indicating PIM6 is a bona fide ligand but other unknown ligands dominate whole-mycobacterium-DC-SIGN interactions. Binding assay with synthetic and natural PIMs, M. bovis BCG pimE mutant and double-knockout (ΔpimE ΔcapA) binding assays to DC-SIGN and DCs, cytokine stimulation assays Infection and immunity High 19651855
2009 DC-SIGN exists in discrete nanoscale clusters on the plasma membrane of dendritic cells, is polarized to the leading edge of the lamellipod, and clusters exhibit two modes of lateral mobility: directed (at ~1420 nm/s toward lamellar sites of internalization) and non-directed. Endocytosis of DC-SIGN clusters occurs preferentially at lamellar sites posterior to the leading edge. Live-cell confocal microscopy, single particle tracking, fluorescence imaging in primary DCs and DC-SIGN transfectants Journal of cell science High 18270264
2009 Surface force measurements show DC-SIGN adopts an extended conformation and that glycan docking is associated with a conformational change that repositions carbohydrate-recognition domains during ligand binding. Lateral mobility of membrane-bound ligands enhances engagement of multiple CRDs in the DC-SIGN oligomer with appropriately spaced ligands. Surface force apparatus measurements between apposed lipid bilayers displaying DC-SIGN ectodomain and neoglycolipid ligands Proceedings of the National Academy of Sciences High 19553201
2011 Several phleboviruses (Rift Valley fever virus, Uukuniemi virus) exploit DC-SIGN as an authentic entry receptor via interactions with high-mannose N-glycans on viral glycoproteins; DC-SIGN is required for both virus internalization and infection. An endocytosis-defective DC-SIGN mutant cannot mediate virus uptake. After internalization, viruses separate from DC-SIGN and traffic to late endosomes. DC-SIGN endocytosis-defective mutant expression, live-cell imaging of virus-receptor interactions, antibody blocking, infection assays in DC-SIGN-expressing cells Cell host & microbe High 21767814
2014 NMR structural characterization of DC-SIGN CRD binding to Lewis X trisaccharide identified residues near the binding site and bound conformations distinct from those in crystal structures; the Le(X) binding mode differs from mannose-terminated saccharide binding. 2D NMR (HSQC chemical shift perturbation), saturation transfer difference NMR, transferred NOE NMR, molecular docking using tetrameric DC-SIGN Biochemistry High 25121780
2014 HHV-8 glycoprotein B (gB) binds DC-SIGN in a dose-dependent manner; gB has high-mannose carbohydrate structure. Key amino acids in the DC-SIGN carbohydrate recognition domain required for HHV-8 infection were identified and differ from the ICAM-2/3 and HIV-1 gp120 binding regions. Dose-dependent binding assays of gB to DC-SIGN, CRD mutagenesis, infection assays, glycan characterization of gB Virus research Medium 25018023
2015 DC-SIGN-expressing macrophages mediate transplantation tolerance; simultaneous DC-SIGN engagement by fucosylated ligands and TLR4 signaling is required for immunoregulatory IL-10 production. Deletion of DC-SIGN-expressing macrophages or interference with DC-SIGN signaling abrogates tolerance. In vivo deletion of DC-SIGN+ macrophages, genetic/pharmacologic interference with DC-SIGN signaling, cytokine production assays, allograft survival experiments Immunity High 26070485
2015 DC-SIGN-expressing macrophages within the follicular lymphoma (FL) microenvironment bind mannosylated IgM BCR on FL B cells, triggering delayed but long-lasting BCR aggregation and activation. M2 macrophages induce DC-SIGN-dependent adhesion of highly mannosylated IgM+ FL B cells and trigger BCR-associated kinase activation. DC-SIGN binding assays to FL B cell BCR, BCR signaling assays, macrophage-FL B cell co-culture assays, pharmacologic BCR inhibitor experiments Blood Medium 26272216
2015 LECT2 (leukocyte cell-derived chemotaxin 2) signals through CD209 (DC-SIGN) to promote JNK phosphorylation in human endothelial cells; CD209 siRNA knockdown abolishes LECT2-induced JNK phosphorylation, ICAM-1 upregulation, and pro-inflammatory cytokine induction. siRNA knockdown of CD209, JNK phosphorylation assays (Western blot), qPCR for ICAM-1 and cytokines, JNK inhibitor experiments in HUVECs and THP-1 cells Metabolism Medium 26123523
2016 DC-SIGN binds specifically to α-fucosylated human milk glycans (HMGs); 2'-fucosyllactose (2'-FL) and 3-fucosyllactose (3-FL) bind DC-SIGN with IC50 of ~1 mM for 2'-FL. No other C-type lectins tested bound HMGs. Glycan microarray screening (>200 HMGs), flow cytometry bead-binding assays with conjugated glycans, competition inhibition assays The Biochemical journal Medium 26976925
2015 In human milk, MUC1 is the major glycoprotein binding to DC-SIGN via Lewis x-type oligosaccharides, and this interaction blocks DC-SIGN-pathogen interactions. This was specific for human milk; formula, bovine, and camel milk did not contain proteins interacting with DC-SIGN. Lectin domain binding assays with human milk fractions, identification of MUC1 as binding partner, competition with pathogens, specificity comparison across milk types Frontiers in immunology Medium 25821450
2019 DC-SIGN-mediated antigen routing is determined by antigen physical properties: soluble glycopolymers are routed to early endosomes, while particulate (aggregated) antigens are diverted to surface-accessible invaginated pockets that also harbor HIV-1, thus avoiding degradation. ROMP-synthesized glycopolymers with varying length/size, confocal microscopy colocalization with endosomal markers, live-cell trafficking assays, comparison with HIV-1 routing Proceedings of the National Academy of Sciences High 31270240
2019 DC-SIGN interacts physically with Lyn kinase; DC-SIGN activation recruits Lyn and p85 to form a DC-SIGN-Lyn-p85 complex, promoting CRC metastasis via PI3K/Akt/β-catenin signaling in a Lyn-dependent manner. This leads to MMP-9 and VEGF transcription and TCF1/LEF1-mediated suppression of miR-185. Co-immunoprecipitation (DC-SIGN-Lyn-p85 complex), gain-of-function/loss-of-function assays, PI3K/Akt/β-catenin pathway assays, miR-185 expression, in vitro and in vivo metastasis assays Cell death and differentiation Medium 31217502
2021 CD209 (DC-SIGN) interacts with the SARS-CoV-2 spike receptor-binding domain (S-RBD) and mediates SARS-CoV-2 entry into human endothelial cells; knockdown of CD209 or use of soluble CD209 inhibits virus entry. CD209 functions as an alternative receptor for SARS-CoV-2 in cells with low or absent ACE2. Biochemical binding assays (purified recombinant S-RBD and ectopically expressed CD209), siRNA knockdown, soluble CD209 inhibition, virus entry assays in human endothelial cells ACS central science High 34341769
2010 IL-4 is the primary inducer of DC-SIGN expression during monocyte-to-DC differentiation; GM-CSF cooperates with IL-4 for high-level expression. IFN-α, IFN-γ, TGF-β, and dexamethasone are negative regulators that prevent IL-4-dependent DC-SIGN induction and inhibit DC-SIGN-dependent HIV-1 binding. DC-SIGN-specific mAb detection, monocyte differentiation assays with various cytokines, mRNA quantification, HIV-1 binding inhibition assays Journal of immunology Medium 11884427
2010 IL-4 regulates DC-SIGN (CD209) expression on human Schwann cells; IL-4 increases CD209 expression and subsequent M. leprae binding to Schwann cells. Th1 cytokines do not induce CD209 on Schwann cells. CD209-positive Schwann cells show higher M. leprae binding than CD209-negative Schwann cells. Primary Schwann cell cultures, IL-4 treatment, M. leprae binding assays comparing CD209+ vs CD209- cells, immunohistochemistry on nerve biopsies Infection and immunity Medium 20713631
2014 The neck domain of DC-SIGN, not the carbohydrate recognition domain (CRD), renders DC-SIGN higher binding affinity to HIV gp120 likely via tetramerization; DC-SIGN has better HIV-1 capture and transfer capability than DCIR. Soluble DC-SIGN/DCIR truncates and chimeras, comparative capture and transfer assays with a wide range of HIV-1 isolates, transfected cell lines Virology Medium 24928041
2021 A secondary binding pocket remote from DC-SIGN's carbohydrate binding site can accommodate aromatic aglycone moieties of glycomimetics, and engagement of this pocket leads to allosteric enhancement of glycan recognition, enabling heteromultivalent cell targeting specific to DC-SIGN+ cells. NMR spectroscopy, molecular docking, molecular dynamics simulations, heteromultivalent liposome cell-binding assays in DC-SIGN+ vs Langerin+ cell lines Journal of the American Chemical Society Medium 34748320
2019 19F-NMR identifies a new binding mode where mannose coordinates a Ca2+ ion in the DC-SIGN CRD lectin carbohydrate recognition domain through axial OH-2 and equatorial OH-3 groups, mimicking the fucose/DC-SIGN binding architecture. Fucose binds with highest affinity among monosaccharides tested (Fuc > Man > Glc > Gal). 19F-NMR competitive binding assays, 1H-STD-NMR, molecular dynamics simulations using purified DC-SIGN CRD Molecules Medium 31242623

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell 1890 10721995
2003 Mycobacteria target DC-SIGN to suppress dendritic cell function. The Journal of experimental medicine 797 12515809
2003 DC-SIGN: escape mechanism for pathogens. Nature reviews. Immunology 698 12949494
2003 DC-SIGN (CD209) mediates dengue virus infection of human dendritic cells. The Journal of experimental medicine 672 12682107
2002 The dendritic cell-specific adhesion receptor DC-SIGN internalizes antigen for presentation to T cells. Journal of immunology (Baltimore, Md. : 1950) 504 11859097
2010 Microbial stimulation fully differentiates monocytes to DC-SIGN/CD209(+) dendritic cells for immune T cell areas. Cell 483 21029863
2003 DC-SIGN is the major Mycobacterium tuberculosis receptor on human dendritic cells. The Journal of experimental medicine 465 12515819
2000 DC-SIGN-ICAM-2 interaction mediates dendritic cell trafficking. Nature immunology 395 11017109
2003 DC-SIGN and DC-SIGNR bind ebola glycoproteins and enhance infection of macrophages and endothelial cells. Virology 299 12504546
2003 The C-type lectin DC-SIGN (CD209) is an antigen-uptake receptor for Candida albicans on dendritic cells. European journal of immunology 296 12645952
2003 Hepatitis C virus glycoproteins interact with DC-SIGN and DC-SIGNR. Journal of virology 294 12634366
2002 DC-SIGN (CD209) expression is IL-4 dependent and is negatively regulated by IFN, TGF-beta, and anti-inflammatory agents. Journal of immunology (Baltimore, Md. : 1950) 225 11884427
2000 DC-SIGN; a related gene, DC-SIGNR; and CD23 form a cluster on 19p13. Journal of immunology (Baltimore, Md. : 1950) 215 10975799
2021 CD209L/L-SIGN and CD209/DC-SIGN Act as Receptors for SARS-CoV-2. ACS central science 213 34341769
2006 DC-SIGN and CLEC-2 mediate human immunodeficiency virus type 1 capture by platelets. Journal of virology 205 16940507
2011 DC-SIGN as a receptor for phleboviruses. Cell host & microbe 194 21767814
2010 C-type lectin DC-SIGN: an adhesion, signalling and antigen-uptake molecule that guides dendritic cells in immunity. Cellular signalling 193 20363321
2006 DC-SIGN ligation on dendritic cells results in ERK and PI3K activation and modulates cytokine production. Blood 187 16434485
2004 L-SIGN (CD209L) and DC-SIGN (CD209) mediate transinfection of liver cells by hepatitis C virus. Proceedings of the National Academy of Sciences of the United States of America 160 15371595
2015 DC-SIGN(+) Macrophages Control the Induction of Transplantation Tolerance. Immunity 155 26070485
2006 DC-SIGN is a receptor for human herpesvirus 8 on dendritic cells and macrophages. Journal of immunology (Baltimore, Md. : 1950) 151 16424204
2013 The physiological role of DC-SIGN: a tale of mice and men. Trends in immunology 149 23608151
2006 Promoter variation in the DC-SIGN-encoding gene CD209 is associated with tuberculosis. PLoS medicine 148 16379498
2003 DC-SIGN promotes exogenous MHC-I-restricted HIV-1 antigen presentation. Blood 145 14576049
2007 DC-SIGN (CD209), pentraxin 3 and vitamin D receptor gene variants associate with pulmonary tuberculosis risk in West Africans. Genes and immunity 143 17611589
2003 DC-SIGN: a novel HIV receptor on DCs that mediates HIV-1 transmission. Current topics in microbiology and immunology 143 12797442
2008 Innate signaling by the C-type lectin DC-SIGN dictates immune responses. Cancer immunology, immunotherapy : CII 125 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 119 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
2008 DC-SIGN and L-SIGN: the SIGNs for infection. Journal of molecular medicine (Berlin, Germany) 117 18458800
2006 Measles virus targets DC-SIGN to enhance dendritic cell infection. Journal of virology 115 16537615
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
2015 DC-SIGN-expressing macrophages trigger activation of mannosylated IgM B-cell receptor in follicular lymphoma. Blood 108 26272216
2003 Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a pathogen receptor with broad specificity. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 98 12974773
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
2001 Extensive repertoire of membrane-bound and soluble dendritic cell-specific ICAM-3-grabbing nonintegrin 1 (DC-SIGN1) and DC-SIGN2 isoforms. Inter-individual variation in expression of DC-SIGN transcripts. The Journal of biological chemistry 91 11337487
2021 CD209L/L-SIGN and CD209/DC-SIGN act as receptors for SARS-CoV-2. bioRxiv : the preprint server for biology 90 32607506
2002 Quantitative expression and virus transmission analysis of DC-SIGN on monocyte-derived dendritic cells. Journal of virology 87 12186897
2009 The DC-SIGN of zebrafish: insights into the existence of a CD209 homologue in a lower vertebrate and its involvement in adaptive immunity. Journal of immunology (Baltimore, Md. : 1950) 84 19890038
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
2003 Cell type-dependent retention and transmission of HIV-1 by DC-SIGN. International immunology 72 12578859
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
2003 A fatal attraction: Mycobacterium tuberculosis and HIV-1 target DC-SIGN to escape immune surveillance. Trends in molecular medicine 67 12727141
2020 C-type Lectin CD209L/L-SIGN and CD209/DC-SIGN: Cell Adhesion Molecules Turned to Pathogen Recognition Receptors. Biology 64 33375175
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
2016 Differential Use of the C-Type Lectins L-SIGN and DC-SIGN for Phlebovirus Endocytosis. Traffic (Copenhagen, Denmark) 59 26990254
2006 Lentivirus degradation and DC-SIGN expression by human platelets and megakaryocytes. Journal of thrombosis and haemostasis : JTH 59 16420576
2013 DC-SIGN, DC-SIGNR and LSECtin: C-type lectins for infection. International reviews of immunology 56 24156700
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
2008 Porcine DC-SIGN: molecular cloning, gene structure, tissue distribution and binding characteristics. Developmental and comparative immunology 56 18951915
2004 The dendritic cell receptor DC-SIGN discriminates among species and life cycle forms of Leishmania. Journal of immunology (Baltimore, Md. : 1950) 54 14707095
2015 LECT2 induces atherosclerotic inflammatory reaction via CD209 receptor-mediated JNK phosphorylation in human endothelial cells. Metabolism: clinical and experimental 53 26123523
2009 DC-SIGN and mannosylated surface structures of Mycobacterium tuberculosis: a deceptive liaison. European journal of cell biology 50 19892432
2008 Distribution and lateral mobility of DC-SIGN on immature dendritic cells--implications for pathogen uptake. Journal of cell science 49 18270264
2019 Antigen structure affects cellular routing through DC-SIGN. Proceedings of the National Academy of Sciences of the United States of America 48 31270240
2014 Structural characterization of the DC-SIGN-Lewis(X) complex. Biochemistry 48 25121780
2007 The C type lectins DC-SIGN and L-SIGN: receptors for viral glycoproteins. Methods in molecular biology (Clifton, N.J.) 48 17502670
2006 DC-SIGN (CD209) recognition of Neisseria gonorrhoeae is circumvented by lipooligosaccharide variation. Journal of leukocyte biology 48 16461738
2003 HIV-1 transmission and cytokine-induced expression of DC-SIGN in human monocyte-derived macrophages. Journal of leukocyte biology 48 12960240
2017 Beyond attachment: Roles of DC-SIGN in dengue virus infection. Traffic (Copenhagen, Denmark) 47 28128492
2012 Noncarbohydrate glycomimetics and glycoprotein surrogates as DC-SIGN antagonists and agonists. ACS chemical biology 44 22747463
2003 Novel member of the CD209 (DC-SIGN) gene family in primates. Journal of virology 43 12477827
2008 Dermal-type macrophages expressing CD209/DC-SIGN show inherent resistance to dengue virus growth. PLoS neglected tropical diseases 41 18827881
2022 CD209/CD14+ Dendritic Cells Characterization in Rheumatoid and Psoriatic Arthritis Patients: Activation, Synovial Infiltration, and Therapeutic Targeting. Frontiers in immunology 40 35095831
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 The evolutionary history of the CD209 (DC-SIGN) family in humans and non-human primates. Genes and immunity 40 18528403
2015 Human Milk Blocks DC-SIGN-Pathogen Interaction via MUC1. Frontiers in immunology 39 25821450
2002 Distribution and immunophenotype of DC-SIGN-expressing cells in SIV-infected and uninfected macaques. AIDS research and human retroviruses 37 12396454
2016 Phenotype and Function of CD209+ Bovine Blood Dendritic Cells, Monocyte-Derived-Dendritic Cells and Monocyte-Derived Macrophages. PloS one 35 27764236
2006 Functional comparison of mouse CIRE/mouse DC-SIGN and human DC-SIGN. International immunology 35 16569675
2007 Structural requirements for multimerization of the pathogen receptor dendritic cell-specific ICAM3-grabbing non-integrin (CD209) on the cell surface. The Journal of biological chemistry 34 18073208
2003 Cyclic nucleotides promote monocyte differentiation toward a DC-SIGN+ (CD209) intermediate cell and impair differentiation into dendritic cells. Journal of immunology (Baltimore, Md. : 1950) 34 14662841
2001 DC-SIGN, a dentritic cell-specific HIV-1 receptor present in placenta that infects T cells in trans-a review. Placenta 34 11312623
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
2012 DC-SIGN antagonists, a potential new class of anti-infectives. Current medicinal chemistry 31 22257062
2010 CD209 (DC-SIGN) -336A>G promoter polymorphism and severe acute respiratory syndrome in Hong Kong Chinese. Human immunology 31 20359516
2010 Targeting DC-SIGN with carbohydrate multivalent systems. Drug news & perspectives 31 21152451
2011 Role of DC-SIGN and L-SIGN receptors in HIV-1 vertical transmission. Human immunology 30 21277928
2005 Role of the C-type lectins DC-SIGN and L-SIGN in Leishmania interaction with host phagocytes. Immunobiology 28 16164025
2003 Isolation and characterization of the human DC-SIGN and DC-SIGNR promoters. Gene 28 12957386
2014 DC-SIGN plays a stronger role than DCIR in mediating HIV-1 capture and transfer. Virology 26 24928041
2010 Relationship between polymorphism of DC-SIGN (CD209) gene and the susceptibility to pulmonary tuberculosis in an eastern Chinese population. Human immunology 26 21081145
2021 A Remote Secondary Binding Pocket Promotes Heteromultivalent Targeting of DC-SIGN. Journal of the American Chemical Society 25 34748320
2015 DC-SIGN expression on podocytes and its role in inflammatory immune response of lupus nephritis. Clinical and experimental immunology 25 26440060
2008 CD209(+) macrophages mediate host defense against Propionibacterium acnes. Journal of immunology (Baltimore, Md. : 1950) 25 18354216
2020 Lipopolysaccharide-induced DC-SIGN/TLR4 crosstalk activates NLRP3 inflammasomes via MyD88-independent signaling in gastric epithelial cells. Experimental cell research 24 32961144
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
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
2014 Monovalent mannose-based DC-SIGN antagonists: targeting the hydrophobic groove of the receptor. European journal of medicinal chemistry 22 24556146
2006 Relevance of DC-SIGN in DC-induced T cell proliferation. Journal of leukocyte biology 22 17135574

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