Affinage

SIGLEC1

Sialoadhesin · UniProt Q9BZZ2

Length
1709 aa
Mass
182.6 kDa
Annotated
2026-04-28
100 papers in source corpus 31 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SIGLEC1 (CD169/sialoadhesin) is a macrophage- and dendritic cell-restricted I-type lectin that recognizes α2,3-linked sialic acids on gangliosides (particularly GM3), functioning as an endocytic and adhesion receptor that captures extracellular vesicles, pathogens, and sialylated cells to orchestrate innate and adaptive immune responses. SIGLEC1 mediates clathrin-dependent endocytosis targeting cargo to early endosomes, and captures ganglioside-bearing enveloped viruses (HIV-1, MLV, Ebola, SARS-CoV-2) into non-lysosomal virus-containing compartments formed at plasma membrane invaginations, enabling trans-infection of lymphocytes via virological synapses (PMID:23271952, PMID:28129379, PMID:36279285, PMID:31160823). Transcriptionally induced by type I interferons through JAK/STAT1 signaling and post-transcriptionally regulated by miR-27a, SIGLEC1 signals via the adaptor DAP12 to recruit SHP2 and Syk, and promotes TRIM27-mediated K48-linked ubiquitination and degradation of TBK1, thereby feedback-suppressing type I IFN production (PMID:26358190, PMID:26700765, PMID:27129263). On subcapsular sinus and marginal zone macrophages, SIGLEC1 captures blood-borne antigens and exosomes via sialic acid recognition, facilitates antigen transfer to BATF3-dependent cDC1s for CD8+ T cell cross-priming, enables iNKT cell activation by lipid antigens, and provides anchorage to hypersialylated metastatic tumor cells (PMID:24255917, PMID:29425504, PMID:23610394, PMID:31872800).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2000 Medium

    Ultrastructural localization established that sialoadhesin resides at macrophage–lymphocyte contact zones and in intracellular vesicles, providing the first evidence for dual roles in cell adhesion and endocytosis.

    Evidence Immunoelectron microscopy on rodent lymph node and spleen sections

    PMID:11131149

    Open questions at the time
    • Single imaging method without functional confirmation
    • Molecular mechanism of internalization unknown
    • Ligands on contacting lymphocytes uncharacterized
  2. 2011 High

    The endocytic mechanism of CD169 was resolved: internalization is clathrin- and Eps15-dependent and routes cargo to early endosomes rather than lysosomes, explaining how captured material avoids degradation.

    Evidence Chemical inhibitors, dominant-negative constructs, and immunofluorescence in porcine macrophages and recombinant cells

    PMID:21359217

    Open questions at the time
    • Porcine system; pathway conservation in human cells not fully demonstrated
    • Cytoplasmic tail motifs mediating sorting uncharacterized
  3. 2012 High

    CD169 was identified as the key receptor mediating HIV-1 capture on dendritic cells through recognition of GM3 ganglioside on viral membranes rather than viral glycoproteins, establishing a glycolipid-dependent, gp120-independent capture mechanism and trans-infection pathway.

    Evidence siRNA knockdown, neutralizing antibodies, exogenous expression rescue, ganglioside depletion from virions, and co-localization imaging

    PMID:23271952 PMID:23593001

    Open questions at the time
    • Structural basis of GM3-CD169 interaction at atomic level unresolved
    • Relative contribution of CD169 versus DC-SIGN in physiological settings uncertain
  4. 2012 High

    CD169 was validated as a functional antigen-delivery receptor: sialic acid-decorated liposomes are internalized exclusively by Sn-expressing macrophages and processed for T cell antigen presentation, absent in Sn-knockout cells.

    Evidence Liposomal nanoparticle uptake assays with Sn-/- macrophages and T cell proliferation readout

    PMID:22723922

    Open questions at the time
    • Antigen processing pathway downstream of early endosomal delivery not mapped
    • Whether MHC-I or MHC-II presentation predominates undetermined
  5. 2013 High

    CD169+ macrophages were shown to capture B cell-derived exosomes in vivo via α2,3-sialic acids, controlling exosome distribution in lymphoid tissues; CD169 knockout altered exosomal distribution and augmented immune responses to exosomal antigen.

    Evidence In vitro binding assays, CD169-/- knockout mice, in vivo exosome tracking in spleen and lymph node

    PMID:24255917

    Open questions at the time
    • Whether exosome capture is tolerogenic or immunogenic context-dependent not resolved
    • Fate of captured exosomes (degraded vs. transferred) unclear
  6. 2013 High

    CD169-mediated lipid antigen delivery was shown to be sufficient for systemic iNKT cell activation, establishing CD169+ macrophages as a critical antigen-presenting niche for lipid immunity.

    Evidence Cd169-/- mice, targeted liposome delivery, macrophage depletion, in vivo iNKT activation readout

    PMID:23610394

    Open questions at the time
    • CD1d loading mechanism downstream of CD169-mediated uptake uncharacterized
    • Whether this pathway operates for endogenous lipid antigens unclear
  7. 2014 High

    Using artificial virus nanoparticles lacking all viral proteins, the GM3–CD169 interaction alone was shown to be sufficient for sequestration of particles into non-lysosomal tetraspanin-positive compartments, definitively separating the ganglioside recognition mechanism from any viral glycoprotein contribution.

    Evidence Artificial virus nanoparticles with defined lipid composition in CD169-expressing HeLa cells and mature DCs

    PMID:24947940

    Open questions at the time
    • Tetraspanin identity and role in compartment formation not determined
    • Whether compartment fate differs between reconstituted and physiological systems
  8. 2015 High

    Three advances defined the VCC biology and signaling axis: (1) CD169 drives formation of virus-containing compartments (VCCs) from plasma membrane invaginations, protecting virus from neutralizing antibodies; (2) the cytoplasmic tail is dispensable for VCC trafficking but an endocytic motif redirects cargo and suppresses trans-infection; (3) CD169 signals through DAP12/SHP2 to recruit TRIM27, which K48-ubiquitinates TBK1 at Lys251/Lys372, degrading it and suppressing type I IFN production.

    Evidence Super-resolution microscopy and tail mutagenesis (VCC); Co-IP, mutagenesis, ubiquitination assays (signaling); intravital microscopy in CD169-/- mice (retroviral spread); sialic acid analog dissection (ligand specificity)

    PMID:25760631 PMID:26358190 PMID:26370074 PMID:26429886

    Open questions at the time
    • How VCC membrane invagination is mechanically generated unknown
    • Whether DAP12-dependent signaling and endocytic/VCC functions are coupled or independent
    • TRIM27 recruitment mechanism downstream of SHP2 not structurally resolved
  9. 2016 High

    Transcriptional and post-transcriptional regulation was mapped: type I IFN induces SIGLEC1 via JAK/STAT1 while simultaneously downregulating miR-27a (which directly targets SIGLEC1 mRNA), creating a feed-forward loop; a human loss-of-function variant (Glu88Ter) confirmed SIGLEC1 is essential for HIV-1 capture and trans-infection ex vivo.

    Evidence miRNA sponge transgenic mice, luciferase reporter assays, human exome analysis of 4,233 HIV-infected individuals with ex vivo functional validation

    PMID:26700765 PMID:27510803

    Open questions at the time
    • Whether Glu88Ter homozygosity has clinical consequences beyond HIV capture unknown
    • Additional transcription factors beyond STAT1 not characterized
  10. 2016 Medium

    CD169's DAP12/Syk signaling axis was linked to TGF-β1 production during endotoxin tolerance, and separately, CD169 knockdown in atherosclerosis-prone mice attenuated lesion formation by reducing monocyte adhesion and oxLDL uptake, extending CD169's functional repertoire beyond infectious disease.

    Evidence Syk inhibitor and KD in RAW264.7 cells (tolerance); lentiviral shRNA in ApoE-/- mice with plaque and chemokine readouts (atherosclerosis)

    PMID:27129263 PMID:27871915

    Open questions at the time
    • Syk-TGF-β1 link demonstrated in cell line only, not primary macrophages
    • Atherosclerosis phenotype from a single lab with shRNA (not genetic KO)
    • Direct ligand on endothelial cells or oxLDL mediating these effects not identified
  11. 2018 High

    CD169's sialic acid-binding domain was shown to mediate direct cell-cell contact with BATF3-dependent CD8α+ dendritic cells, enabling antigen transfer and CD8+ T cell cross-priming — resolving how macrophage-captured antigens reach the cross-presentation pathway.

    Evidence CD169 sialic acid-binding mutants, BATF3-/- and DNGR-1-/- mice, antigen targeting with T cell activation readout

    PMID:29425504

    Open questions at the time
    • Identity of the sialylated ligand on cDC1 surface not determined
    • Whether antigen is transferred as intact protein, peptide-MHC, or membrane fragment unknown
  12. 2019 High

    CD169's pathogen capture role was extended to Ebola virus (ganglioside-dependent uptake blocked by anti-Siglec-1 antibodies), and separately, Siglec-1 on subcapsular sinus macrophages was found to anchor hypersialylated metastatic melanoma cells, promoting their proliferation.

    Evidence Anti-Siglec-1 blocking antibodies with viral entry assays in activated DCs (Ebola); co-culture, GFP-melanoma model, St3gal3 KO (metastasis)

    PMID:31160823 PMID:31872800

    Open questions at the time
    • Whether anti-Siglec-1 antibodies are protective in vivo against Ebola not tested
    • Proliferative signal delivered by Siglec-1 to cancer cells not identified
    • Whether Siglec-1-mediated tumor cell anchorage is α2,3-sialic acid-exclusive
  13. 2020 High

    CD169 was localized to tunneling nanotubes (TNTs) in macrophages, where it enhances HIV-1 capture and cell-to-cell transfer; Mycobacterium tuberculosis co-infection amplifies this through type I IFN-driven CD169 induction, explaining TB-HIV synergy.

    Evidence Siglec-1 depletion, TNT imaging, HIV-1 transfer assays, non-human primate co-infection model

    PMID:32223897

    Open questions at the time
    • Mechanism by which CD169 promotes TNT elongation not resolved
    • Whether TNT-mediated transfer dominates over VCC-synapse transfer quantitatively unclear
  14. 2022 High

    CD169 mediates ACE2-independent SARS-CoV-2 entry into macrophages leading to abortive infection with restricted viral RNA expression that triggers RIG-I/MDA-5/MAVS-dependent pro-inflammatory cytokine production, linking CD169 to COVID-19 macrophage hyperactivation.

    Evidence CD169 expression/knockdown, ACE2 rescue, remdesivir treatment, RIG-I/MDA-5/MAVS pathway inhibition in macrophages

    PMID:36279285

    Open questions at the time
    • Whether CD169-dependent SARS-CoV-2 entry contributes to disease severity in vivo untested
    • Mechanism of post-entry restriction in macrophages not identified
  15. 2022 High

    The differentiation signals for CD169+ macrophage subsets were resolved: dual LTβR and RANK signaling from marginal zone stromal cells is required, and loss of these macrophages compromises viral capture and CD8+ T cell expansion.

    Evidence Conditional receptor ablation (Cd169-directed), RANKL reporter mouse, double haploinsufficiency models, viral challenge

    PMID:35031565

    Open questions at the time
    • Downstream transcription factors linking LTβR/RANK to CD169 expression not identified
    • Whether human CD169+ macrophage differentiation follows the same dual-signal requirement unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of GM3–CD169 recognition at atomic resolution, how VCC membrane invaginations are mechanically generated, the identity of sialylated ligands on cDC1s mediating antigen transfer, and whether the DAP12/Syk signaling and endocytic/VCC functions are mechanistically coupled or independent.
  • No crystal structure of full-length CD169 with GM3 ligand
  • VCC biogenesis mechanism unknown
  • Sialylated cDC1 counter-receptor unidentified
  • Coupling between signaling and trafficking functions unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 5 GO:0038024 cargo receptor activity 3 GO:0060089 molecular transducer activity 2
Localization
GO:0005886 plasma membrane 5 GO:0031410 cytoplasmic vesicle 4 GO:0005576 extracellular region 2
Pathway
R-HSA-1643685 Disease 6 R-HSA-168256 Immune System 6 R-HSA-162582 Signal Transduction 3 R-HSA-5653656 Vesicle-mediated transport 3
Partners
DAP12SHP2SYKTBK1TRIM27

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 Siglec-1 (CD169) on mature dendritic cells specifically binds HIV-1 and vesicles carrying sialyllactose-containing gangliosides (GM3) on the viral membrane, mediating HIV-1 capture and trans-infection of CD4+ T cells through a glycoprotein-independent, ganglioside-dependent pathway. Selective siRNA knockdown of Siglec-1, neutralizing antibodies, exogenous Siglec-1 expression in naive cells, GSL depletion from virions; co-localization imaging of HIV-1 with CD169 on DC surface and in non-lysosomal compartments PLoS biology High 23271952
2013 CD169/Siglec-1 is required for the capture of B cell-derived exosomes via α2,3-linked sialic acids on their surface; CD169-expressing macrophages in the marginal zone of spleen and subcapsular sinus of lymph node capture and retain exosomes, with CD169-/- mice showing altered exosomal distribution and enhanced immune response to exosomal antigen. In vitro binding assays on tissue sections, CD169-/- knockout mice, in vivo exosome tracking Blood High 24255917
2013 Type I IFN-inducible Siglec-1/CD169 on dendritic cells captures HIV-1 in a GM3 ganglioside-dependent manner; captured virus co-localizes with CD169 on DC surface and within non-lysosomal compartments that redistribute to DC-T cell infectious synapses, enabling trans-infection of CD4+ T cells. Selective CD169 downregulation, neutralizing antibodies, exogenous CD169 expression in receptor-naive cells, GSL depletion, co-localization imaging PLoS pathogens High 23593001
2015 Siglec1 associates with DAP12 to recruit and activate SHP2, which then recruits E3 ubiquitin ligase TRIM27; TRIM27 induces K48-linked ubiquitination of TBK1 at Lys251 and Lys372, leading to TBK1 degradation and suppression of type I IFN production in macrophages during viral infection. Co-immunoprecipitation, siRNA knockdown, ubiquitination assays, site-directed mutagenesis of TBK1 ubiquitination sites, overexpression studies Cell research High 26358190
2015 CD169/Siglec-1 on sinus-lining macrophages captures retroviruses (MLV and HIV) via recognition of gangliosides; MLV-laden CD169+ macrophages form long-lived synaptic contacts with B-1 cells to trans-infect them; infected B-1 cells then migrate into lymph nodes to spread infection via virological synapses. Robust lymph node and spleen infection requires CD169. Intravital microscopy in living mice, CD169-/- knockout mice, retroviral infection models Science (New York, N.Y.) High 26429886
2017 Siglec-1 on macrophages initiates formation of the virus-containing compartment (VCC) by capturing ganglioside-containing viral particles from the plasma membrane; Siglec-1 depletion or ganglioside depletion from viral particles prevents VCC formation and substantially reduces VCC volume, and Siglec-1-mediated VCC formation is required for efficient trans-infection of autologous T cells. Siglec-1 depletion (siRNA), non-infectious VLP addition to macrophage cultures, ganglioside depletion, volumetric imaging of VCC PLoS pathogens High 28129379
2015 CD169/Siglec-1-mediated HIV-1 trafficking to deep plasma membrane invaginations (VCCs) protects HIV-1 from antibody-mediated neutralization; the cytoplasmic tail of CD169 is dispensable for HIV-1 trafficking and retention within VCCs, but introduction of a di-aromatic endocytic motif in the tail causes endocytosis and suppresses trans-infection. Super-resolution microscopy, cytoplasmic tail mutagenesis, broadly neutralizing antibody treatment, trans-infection assays PLoS pathogens High 25760631
2014 GM3-CD169 binding is a gp120-independent signal mediating HIV-1 sequestration and preservation of infectivity in non-lysosomal tetraspanin-positive compartments in dendritic cells; this was demonstrated using artificial virus nanoparticles (AVNs) free of viral glycoproteins containing defined GM3 composition. Artificial virus nanoparticles with defined lipid composition, CD169-expressing HeLa cells and mature DCs, compartment co-localization imaging Nature communications High 24947940
2011 Porcine sialoadhesin (CD169) functions as an endocytic receptor; antibody-triggered internalization is clathrin- and Eps15-dependent and targets cargo to early endosomes but not lysosomes. Chemical inhibitors of endocytic pathways, dominant-negative constructs, double immunofluorescence staining, primary porcine macrophages and recombinant CD169-expressing cells PloS one High 21359217
2012 Sialoadhesin (CD169)/Sn-targeted liposomes decorated with high-affinity glycan ligands are selectively internalized by Sn-expressing cells via Sn-mediated endocytosis; uptake is absent in Sn-/- macrophages, and internalized antigen is presented to T cells, demonstrating CD169 as a functional antigen-delivery endocytic receptor. Liposomal nanoparticle binding/uptake assays, Sn-/- knockout macrophages, T cell proliferation assays PloS one High 22723922
2013 CD169/Sn-mediated endocytosis of lipid antigens in CD169+ macrophages enables robust iNKT cell activation in liver and spleen; activation is abrogated in Cd169-/- mice and is macrophage-dependent, demonstrating that targeting CD169+ macrophages is sufficient for systemic iNKT cell activation. Cd169-/- knockout mice, targeted liposome delivery, macrophage depletion, in vivo iNKT activation readout Proceedings of the National Academy of Sciences of the United States of America High 23610394
2015 Mouse Siglec-1 expressed on primary macrophages in an IFN-α-responsive manner captures MLV particles via sialylated gangliosides and mediates trans-infection of B cells more efficiently than T cells; the N-acyl side chain of sialic acid is a critical determinant, with N-butanoyl, N-isobutanoyl, N-glycolyl, or N-pentanoyl modifications reducing virus capture and trans-infection by up to 92% and 80% respectively. Primary macrophage cultures, biosynthetic sialic acid analog incorporation, MLV capture assays, trans-infection assays, molecular modeling The Journal of biological chemistry High 26370074
2019 Siglec-1 on dendritic cells recognizes sialylated gangliosides anchored to Ebola virus membranes, mediating viral uptake and cytoplasmic entry; anti-Siglec-1 monoclonal antibodies block Ebola virus uptake and entry, and provide cross-protection against other ganglioside-containing viruses including HIV-1. Anti-Siglec-1 blocking antibodies, viral uptake and entry assays in activated DCs, cross-protection experiments Nature microbiology High 31160823
2016 Siglec-1 induction in macrophages by endotoxin tolerance suppresses innate immune responses by promoting TGF-β1 production via association with adaptor protein DAP12 and transduction of a signal through Syk; knockdown of Siglec-1 inhibits TGF-β1 production via ubiquitin-dependent degradation of Syk. Siglec-1 knockdown in RAW 264.7 cells, Syk inhibitor, TGF-β1 measurement, co-association studies with DAP12 The Journal of biological chemistry Medium 27129263
2018 CD169 on splenic macrophages mediates cell-cell contact with BATF3-dependent CD8α+ dendritic cells via its sialic acid-binding capacity, enabling antigen transfer to CD8α+ DCs and subsequent CD8+ T cell cross-priming; this interaction and cross-priming is dependent on the functional sialic acid-binding domain of CD169. CD169 sialic acid-binding mutants, BATF3-/- mice, DNGR-1-/- mice, antigen targeting assays, T cell activation readout Cell reports High 29425504
2020 Siglec-1 localizes mainly on microtubule-containing tunneling nanotubes (TNTs) in macrophages; Siglec-1 expression is induced by Mycobacterium tuberculosis-driven type I IFN production, and Siglec-1 depletion decreases TNT length, diminishes HIV-1 capture and cell-to-cell transfer via TNTs, and abrogates the exacerbation of HIV-1 infection induced by Mtb. Siglec-1 depletion, transcriptomic analysis, TNT imaging, HIV-1 transfer assays, non-human primate co-infection model eLife High 32223897
2022 CD169 facilitates ACE2-independent SARS-CoV-2 fusion and entry into macrophages; CD169-mediated SARS-CoV-2 entry results in expression of viral genomic and subgenomic RNAs with minimal viral protein expression and no infectious particle release (post-entry restriction), and restricted viral RNA expression elicits pro-inflammatory cytokine production (TNFα, IL-6, IL-1β) in a RIG-I/MDA-5/MAVS-dependent manner. CD169 expression/knockdown in macrophages, exogenous ACE2 rescue, viral entry assays, remdesivir treatment, RIG-I/MDA-5/MAVS pathway inhibition PLoS pathogens High 36279285
2017 IFN-α-treated myeloid cells (DCs, macrophages) upregulate CD169, which enhances HIV-1 attachment and entry (virus entry step), offsetting the antiviral effects of type I IFN; in DC-T cell cocultures, CD169 on IFNα-treated DCs rescues trans-infection of CD4+ T cells despite IFN-α-induced restriction in T cells. CD169 KD in THP-1 and primary MDMs, IFN-α treatment, HIV-1 infection assays, DC-T cell coculture trans-infection, SIV-infected macaque lymph node immunohistochemistry Journal of virology High 28794041
2019 Siglec-1-expressing subcapsular sinus macrophages provide anchorage to pioneer metastatic melanoma cells via interactions with hypersialylated cancer cells; Siglec-1-cancer cell interaction drives proliferation (enrichment of cell cycle progression genes in Siglec-1-interacting cells), and knockout of St3gal3 sialyltransferase reduces α-2,3-linked sialylation and impairs metastatic efficiency. In vitro co-culture, GFP-melanoma mouse model, transcriptome profiling of Siglec1-interacting vs non-interacting cancer cells, St3gal3 knockout eLife Medium 31872800
2019 Siglec-1 on dendritic cells in the cervical mucosa (lamina propria of ectocervix and endocervix) mediates HIV-1 capture and trans-infection; type I IFN environment enhances viral capture via Siglec-1, and anti-Siglec-1 antibodies prevent HIV-1 transfer. Ex vivo cervical biopsy, anti-Siglec-1 blocking antibodies, in vivo detection of Siglec-1+ cells harboring HIV-1 compartments in viremic patient biopsy Frontiers in immunology Medium 31114569
2019 Pre-DC precursors constitutively express Siglec-1, which promotes attachment and fusion of HIV-1 viral particles and enables productive infection of pre-DCs; Siglec-1 does not counteract restriction factors like SAMHD1 but acts at the viral attachment/fusion step, and infected pre-DCs accumulate new particles in intracellular compartments resembling macrophage VCCs. Siglec-1-dependent infection assays in pre-DCs, HIV-2/SIVmac Vpx rescue, viral particle accumulation imaging Proceedings of the National Academy of Sciences of the United States of America Medium 31591213
2000 Sialoadhesin (Siglec-1) is selectively expressed on the plasma membrane of macrophage subsets, particularly at areas of intimate contact with lymphocytes, and is also detected in intracellular vesicles taken up by macrophages, suggesting roles in cell-cell adhesion and endocytosis. Immunoelectron microscopy on lymph node and spleen sections of rodents Immunobiology Medium 11131149
2006 Sialoadhesin (Siglec-1) expressed on peripheral nerve macrophages promotes CD8+ T lymphocyte accumulation and macrophage activation in demyelinating neuropathy; Siglec-1-deficient P0+/- mice show reduced CD8+ T lymphocytes and macrophages in peripheral nerves and less severe demyelination with improved nerve conduction. Siglec-1/Sn-deficient mouse crossed with P0+/- demyelination model, nerve conduction measurements, flow cytometry and histology Molecular and cellular neurosciences Medium 16458537
2022 CD169+ macrophage differentiation in lymph node and spleen requires dual signals from LTβR and RANK receptors; loss of either receptor perturbs differentiation, and combined haploinsufficiency reveals equal contributions; splenic RANKL originates from marginal zone stromal cells; loss of CD169+ macrophages (MMMs) compromises viral capture and CD8+ T cell expansion. Conditional receptor ablation (Cd169-directed), RANKL reporter mouse, double haploinsufficiency models, viral infection challenge Proceedings of the National Academy of Sciences of the United States of America High 35031565
2018 CD169+ macrophage depletion in murine Friend virus complex infection reduces viral capture at lymph nodes but paradoxically limits systemic spread to spleen; CD169-expressing macrophages capture blood-borne retroviruses and activate cDC1s, promoting cytotoxic CD8+ T cell responses and efficient clearing of infected cells. CD169 blockade leads to higher viral loads and accelerated death. CD169-/- mice, CD169 blockade, intravital imaging, cDC1 activation assays, viral load measurement Cell host & microbe High 30595553
2016 SIGLEC1 expression on macrophages is upregulated by viral infection through the IFN/JAK/STAT1 signaling pathway; miR-27a directly targets Siglec1 mRNA, and type I IFN-induced downregulation of miR-27a leads to upregulation of Siglec1 and TRIM27, which feedback inhibits type I IFN production. miRNA screening in macrophages, miR-27a sponge transgenic mice, luciferase reporter assays for direct targeting, viral infection models (VSV) Journal of immunology (Baltimore, Md. : 1950) High 26700765
2016 SIGLEC1 loss-of-function variant (Glu88Ter) in humans results in cells that are functionally null or haploinsufficient for Siglec-1 activity in HIV-1 capture and trans-infection ex vivo, confirming the essential role of Siglec-1 in these processes at a molecular level. Human exome analysis, direct genotyping of 4,233 HIV-infected individuals, ex vivo HIV-1 capture and trans-infection assays on cells from loss-of-function carriers Nature communications High 27510803
2020 CD169 expression on monocytes is directly induced by type I IFNs (but not type II IFN/IFNγ) via the JAK/STAT signaling pathway within 6-8 hours; IFNα and other type I IFNs specifically upregulate CD169, whereas IFNγ preferentially upregulates CD64, and the two IFN types partially inhibit each other's effects. Whole blood stimulation with purified IFNs, flow cytometry over defined kinetics, JAK/STAT pathway analysis Immunity, inflammation and disease Medium 32031762
2010 Sialoadhesin (CD169) on rhinovirus-activated dendritic cells, together with B7-H1 (CD274), delivers a combinatorial signal to T cells that induces IL-35 production and suppressor function; blocking both CD169 and B7-H1 with antibodies prevents induction of IL-35+ regulatory T cells. Blocking antibodies against CD169 and B7-H1 on DC, IL-35 production assay, T cell suppressor function assay European journal of immunology Medium 19950173
2020 Siglec-1 knockdown in COPD macrophages decreases phagocytosis of non-typeable Haemophilus influenzae (NTHi), demonstrating that Siglec-1 functions as a phagocytic receptor for bacteria on alveolar macrophages. Anti-Siglec-1 blocking antibody on human alveolar macrophages, phagocytosis assay with fluorescence-tagged bacteria Respiratory research Medium 31992280
2016 Knockdown of Siglec-1 in apoE-deficient mice attenuates atherosclerotic lesion formation by suppressing monocyte-endothelial cell adhesion, decreasing chemokine secretion (MCP-1, CXCL2) from aortas and CCR2/CXCR2 expression on monocytes, and reducing macrophage accumulation and oxLDL uptake. Lentiviral shRNA knockdown in Apoe-/- mice, plaque area measurement, cytokine/chemokine measurement, oxLDL uptake assay Clinical immunology (Orlando, Fla.) Medium 27871915

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche. The Journal of experimental medicine 650 21282381
2010 CD169-positive macrophages dominate antitumor immunity by crosspresenting dead cell-associated antigens. Immunity 371 21194983
2013 CD169⁺ macrophages provide a niche promoting erythropoiesis under homeostasis and stress. Nature medicine 351 23502962
2013 CD169 mediates the capture of exosomes in spleen and lymph node. Blood 305 24255917
2012 Siglec-1 is a novel dendritic cell receptor that mediates HIV-1 trans-infection through recognition of viral membrane gangliosides. PLoS biology 198 23271952
2012 Antigen delivery to macrophages using liposomal nanoparticles targeting sialoadhesin/CD169. PloS one 175 22723922
2011 CD169+ macrophages at the crossroads of antigen presentation. Trends in immunology 168 22192781
2015 Siglec1 suppresses antiviral innate immune response by inducing TBK1 degradation via the ubiquitin ligase TRIM27. Cell research 159 26358190
2017 CD169+ macrophages are critical for osteoblast maintenance and promote intramembranous and endochondral ossification during bone repair. Biomaterials 148 29107337
2015 Retroviruses use CD169-mediated trans-infection of permissive lymphocytes to establish infection. Science (New York, N.Y.) 144 26429886
2013 Interferon-inducible mechanism of dendritic cell-mediated HIV-1 dissemination is dependent on Siglec-1/CD169. PLoS pathogens 140 23593001
2018 Functional CD169 on Macrophages Mediates Interaction with Dendritic Cells for CD8+ T Cell Cross-Priming. Cell reports 106 29425504
2013 An intact sialoadhesin (Sn/SIGLEC1/CD169) is not required for attachment/internalization of the porcine reproductive and respiratory syndrome virus. Journal of virology 103 23785195
2013 Targeted delivery of lipid antigen to macrophages via the CD169/sialoadhesin endocytic pathway induces robust invariant natural killer T cell activation. Proceedings of the National Academy of Sciences of the United States of America 102 23610394
2018 CD169+ Macrophages Capture and Dendritic Cells Instruct: The Interplay of the Gatekeeper and the General of the Immune System. Frontiers in immunology 100 30416504
2016 Central Role of CD169+ Lymph Node Resident Macrophages in the Adjuvanticity of the QS-21 Component of AS01. Scientific reports 100 27996000
2014 Marginal zone CD169+ macrophages coordinate apoptotic cell-driven cellular recruitment and tolerance. Proceedings of the National Academy of Sciences of the United States of America 95 24591636
2014 HIV-1 capture and transmission by dendritic cells: the role of viral glycolipids and the cellular receptor Siglec-1. PLoS pathogens 94 25033082
2014 Vascular-resident CD169-positive monocytes and macrophages control neutrophil accumulation in the kidney with ischemia-reperfusion injury. Journal of the American Society of Nephrology : JASN 87 25266072
2012 Subcapsular sinus macrophage fragmentation and CD169+ bleb acquisition by closely associated IL-17-committed innate-like lymphocytes. PloS one 80 22675532
2017 Siglec-1 initiates formation of the virus-containing compartment and enhances macrophage-to-T cell transmission of HIV-1. PLoS pathogens 76 28129379
2010 Human rhinoviruses induce IL-35-producing Treg via induction of B7-H1 (CD274) and sialoadhesin (CD169) on DC. European journal of immunology 76 19950173
2015 HIV-1 immune activation induces Siglec-1 expression and enhances viral trans-infection in blood and tissue myeloid cells. Retrovirology 75 25947229
2014 Mobilization with granulocyte colony-stimulating factor blocks medullar erythropoiesis by depleting F4/80(+)VCAM1(+)CD169(+)ER-HR3(+)Ly6G(+) erythroid island macrophages in the mouse. Experimental hematology 75 24721610
2011 Porcine sialoadhesin (CD169/Siglec-1) is an endocytic receptor that allows targeted delivery of toxins and antigens to macrophages. PloS one 73 21359217
2022 Blood monocyte-derived CD169+ macrophages contribute to antitumor immunity against glioblastoma. Nature communications 72 36266311
2016 Tissue-Resident CD169(+) Macrophages Form a Crucial Front Line against Plasmodium Infection. Cell reports 69 27477286
2020 Selective tumor antigen vaccine delivery to human CD169+ antigen-presenting cells using ganglioside-liposomes. Proceedings of the National Academy of Sciences of the United States of America 67 33067394
2016 CD169 identifies an anti-tumour macrophage subpopulation in human hepatocellular carcinoma. The Journal of pathology 67 27174787
2015 CD169-mediated trafficking of HIV to plasma membrane invaginations in dendritic cells attenuates efficacy of anti-gp120 broadly neutralizing antibodies. PLoS pathogens 65 25760631
2005 The sialoadhesin (CD169) expressing a macrophage subset in human proliferative glomerulonephritis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 61 16169862
2014 Glycosphingolipid-functionalized nanoparticles recapitulate CD169-dependent HIV-1 uptake and trafficking in dendritic cells. Nature communications 59 24947940
2019 Breast cancer cells promote CD169+ macrophage-associated immunosuppression through JAK2-mediated PD-L1 upregulation on macrophages. International immunopharmacology 57 31865052
2013 Increased expression of Siglec-1 on peripheral blood monocytes and its role in mononuclear cell reactivity to autoantigen in rheumatoid arthritis. Rheumatology (Oxford, England) 57 24196391
2021 CD169+ lymph node macrophages have protective functions in mouse breast cancer metastasis. Cell reports 54 33852863
2016 CD169+ macrophages regulate PD-L1 expression via type I interferon and thereby prevent severe immunopathology after LCMV infection. Cell death & disease 54 27809306
2021 Monocyte CD169 Expression as a Biomarker in the Early Diagnosis of Coronavirus Disease 2019. The Journal of infectious diseases 52 33206973
2020 Tuberculosis-associated IFN-I induces Siglec-1 on tunneling nanotubes and favors HIV-1 spread in macrophages. eLife 52 32223897
2015 Antigen targeting reveals splenic CD169+ macrophages as promoters of germinal center B-cell responses. European journal of immunology 51 25487358
2021 CD169 Defines Activated CD14+ Monocytes With Enhanced CD8+ T Cell Activation Capacity. Frontiers in immunology 49 34394090
2014 The identification and developmental requirements of colonic CD169⁺ macrophages. Immunology 47 24883436
2016 SIGLEC1 is a biomarker of disease activity and indicates extraglandular manifestation in primary Sjögren's syndrome. RMD open 46 28123773
2019 Anti-Siglec-1 antibodies block Ebola viral uptake and decrease cytoplasmic viral entry. Nature microbiology 45 31160823
2018 The plasma biomarker soluble SIGLEC-1 is associated with the type I interferon transcriptional signature, ethnic background and renal disease in systemic lupus erythematosus. Arthritis research & therapy 44 30053827
2018 Targeted Delivery of Antigen to Activated CD169+ Macrophages Induces Bias for Expansion of CD8+ T Cells. Cell chemical biology 44 30393066
2017 Interferon-Inducible CD169/Siglec1 Attenuates Anti-HIV-1 Effects of Alpha Interferon. Journal of virology 42 28794041
2022 Siglec-1 expression on monocytes is associated with the interferon signature in juvenile dermatomyositis and can predict treatment response. Rheumatology (Oxford, England) 41 34387304
2019 Dendritic Cells From the Cervical Mucosa Capture and Transfer HIV-1 via Siglec-1. Frontiers in immunology 41 31114569
2005 CD14 and CD169 expression in human lymph nodes and spleen: specific expansion of CD14+CD169- monocyte-derived cells in diffuse large B-cell lymphomas. Human pathology 41 16360418
2022 CD169-mediated restrictive SARS-CoV-2 infection of macrophages induces pro-inflammatory responses. PLoS pathogens 40 36279285
2020 Role of the interferons in CD64 and CD169 expressions in whole blood: Relevance in the balance between viral- or bacterial-oriented immune responses. Immunity, inflammation and disease 40 32031762
2018 Siglec-1 Macrophages and the Contribution of IFN to the Development of Autoimmune Congenital Heart Block. Journal of immunology (Baltimore, Md. : 1950) 40 30518570
2017 High maternal expression of SIGLEC1 on monocytes as a surrogate marker of a type I interferon signature is a risk factor for the development of autoimmune congenital heart block. Annals of the rheumatic diseases 40 28501799
2019 Constitutive Siglec-1 expression confers susceptibility to HIV-1 infection of human dendritic cell precursors. Proceedings of the National Academy of Sciences of the United States of America 38 31591213
2016 Induction of Siglec-1 by Endotoxin Tolerance Suppresses the Innate Immune Response by Promoting TGF-β1 Production. The Journal of biological chemistry 38 27129263
2021 Type I IFNs repolarized a CD169+ macrophage population with anti-tumor potentials in hepatocellular carcinoma. Molecular therapy : the journal of the American Society of Gene Therapy 37 34563673
2017 Reduced number of CD169+ macrophages in pre-metastatic regional lymph nodes is associated with subsequent metastatic disease in an animal model and with poor outcome in prostate cancer patients. The Prostate 37 28880401
2015 Type I IFN-Inducible Downregulation of MicroRNA-27a Feedback Inhibits Antiviral Innate Response by Upregulating Siglec1/TRIM27. Journal of immunology (Baltimore, Md. : 1950) 37 26700765
2019 Siglec1-expressing subcapsular sinus macrophages provide soil for melanoma lymph node metastasis. eLife 34 31872800
2017 CD169 is a marker for highly pathogenic phagocytes in multiple sclerosis. Multiple sclerosis (Houndmills, Basingstoke, England) 34 28277099
2015 The CD169 sialoadhesin molecule mediates cytotoxic T-cell responses to tumour apoptotic vesicles. Immunology and cell biology 34 26647968
2014 CD169-dependent cell-associated HIV-1 transmission: a driver of virus dissemination. The Journal of infectious diseases 32 25414418
2006 Attenuated demyelination in the absence of the macrophage-restricted adhesion molecule sialoadhesin (Siglec-1) in mice heterozygously deficient in P0. Molecular and cellular neurosciences 32 16458537
2022 Naringenin potentiates anti-tumor immunity against oral cancer by inducing lymph node CD169-positive macrophage activation and cytotoxic T cell infiltration. Cancer immunology, immunotherapy : CII 31 35044489
2022 Myeloid CD169/Siglec1: An immunoregulatory biomarker in viral disease. Frontiers in medicine 31 36213653
2022 SIGLEC1 enables straightforward assessment of type I interferon activity in idiopathic inflammatory myopathies. RMD open 30 35177553
2015 Mouse Siglec-1 Mediates trans-Infection of Surface-bound Murine Leukemia Virus in a Sialic Acid N-Acyl Side Chain-dependent Manner. The Journal of biological chemistry 30 26370074
2015 Increased Expression of CD169 on Blood Monocytes and Its Regulation by Virus and CD8 T Cells in Macaque Models of HIV Infection and AIDS. AIDS research and human retroviruses 29 25891017
2021 Liposomal Nanovaccine Containing α-Galactosylceramide and Ganglioside GM3 Stimulates Robust CD8+ T Cell Responses via CD169+ Macrophages and cDC1. Vaccines 28 33467048
2020 SIGLEC1 (CD169) is a sensitive biomarker for the deterioration of the clinical course in childhood systemic lupus erythematosus. Lupus 28 33081587
2019 Activation of CD8⁺ T Cell Responses after Melanoma Antigen Targeting to CD169⁺ Antigen Presenting Cells in Mice and Humans. Cancers 27 30764534
2018 A Protective Role for the Lectin CD169/Siglec-1 against a Pathogenic Murine Retrovirus. Cell host & microbe 27 30595553
2016 Identification of Siglec-1 null individuals infected with HIV-1. Nature communications 26 27510803
2019 Low Dose of Cyanidin-3-O-Glucoside Alleviated Dextran Sulfate Sodium-Induced Colitis, Mediated by CD169+ Macrophage Pathway. Inflammatory bowel diseases 25 31107535
2017 Transient Depletion of CD169+ Cells Contributes to Impaired Early Protection and Effector CD8+ T Cell Recruitment against Mucosal Respiratory Syncytial Virus Infection. Frontiers in immunology 25 28751894
2023 Breast cancer associated CD169+ macrophages possess broad immunosuppressive functions but enhance antibody secretion by activated B cells. Frontiers in immunology 24 37404831
2022 CD169+ macrophages in lymph node and spleen critically depend on dual RANK and LTbetaR signaling. Proceedings of the National Academy of Sciences of the United States of America 24 35031565
2021 Liposome induction of CD8+ T cell responses depends on CD169+ macrophages and Batf3-dependent dendritic cells and is enhanced by GM3 inclusion. Journal of controlled release : official journal of the Controlled Release Society 24 33493613
2021 The role of sialic acid-binding immunoglobulin-like-lectin-1 (siglec-1) in immunology and infectious disease. International reviews of immunology 24 34494938
2021 SIGLEC1 (CD169): a marker of active neuroinflammation in the brain but not in the blood of multiple sclerosis patients. Scientific reports 23 33986412
2019 When Dendritic Cells Go Viral: The Role of Siglec-1 in Host Defense and Dissemination of Enveloped Viruses. Viruses 23 31861617
2015 Deficiency of the B cell-activating factor receptor results in limited CD169+ macrophage function during viral infection. Journal of virology 23 25673724
2022 Adaptation of African swine fever virus to porcine kidney cells stably expressing CD163 and Siglec1. Frontiers in immunology 22 36389805
2020 Decreased expression of a phagocytic receptor Siglec-1 on alveolar macrophages in chronic obstructive pulmonary disease. Respiratory research 22 31992280
2020 Optimization of Liposomes for Antigen Targeting to Splenic CD169+ Macrophages. Pharmaceutics 22 33255564
2018 Comparison of Protein and Peptide Targeting for the Development of a CD169-Based Vaccination Strategy Against Melanoma. Frontiers in immunology 21 30237798
2018 High CD169 expression in lymph node macrophages predicts a favorable clinical course in patients with esophageal cancer. Pathology international 21 30516869
2023 CD169 expression on monocytes as a marker for assessing type I interferon status in pediatric inflammatory diseases. Clinical immunology (Orlando, Fla.) 19 37061149
2016 Relationships of CD163 and CD169 positive cell numbers in the endometrium and fetal placenta with type 2 PRRSV RNA concentration in fetal thymus. Veterinary research 19 27494990
2021 Monocyte CD169 expression in COVID-19 patients upon intensive care unit admission. Cytometry. Part A : the journal of the International Society for Analytical Cytology 18 33547747
2020 MiR-195-5p inhibits the development of chronic obstructive pulmonary disease via targeting siglec1. Human & experimental toxicology 18 32351126
2018 Tumor Necrosis Factor-Mediated Survival of CD169+ Cells Promotes Immune Activation during Vesicular Stomatitis Virus Infection. Journal of virology 18 29142134
2012 SIGLEC1 and SIGLEC7 expression in circulating monocytes of patients with multiple sclerosis. Multiple sclerosis (Houndmills, Basingstoke, England) 18 22933622
2021 Validation of a Quick Flow Cytometry-Based Assay for Acute Infection Based on CD64 and CD169 Expression. New Tools for Early Diagnosis in COVID-19 Pandemic. Frontiers in medicine 17 33869256
2016 Siglec-1 and -2 as potential biomarkers in autoimmune disease. Proteomics. Clinical applications 17 26752092
2012 Contribution of monocytes Siglec-1 in stimulating T cells proliferation and activation in atherosclerosis. Atherosclerosis 17 22789514
2010 Increased Siglec-1 expression in monocytes of patients with primary biliary cirrhosis. Immunological investigations 17 20653431
2016 Inhibition of siglec-1 by lentivirus mediated small interfering RNA attenuates atherogenesis in apoE-deficient mice. Clinical immunology (Orlando, Fla.) 16 27871915
2013 Phenotypic and functional heterogeneity of CD169⁺ and CD163⁺ macrophages from porcine lymph nodes and spleen. Developmental and comparative immunology 16 24291017
2000 Ultrastructural localisation of sialoadhesin (siglec-1) on macrophages in rodent lymphoid tissues. Immunobiology 16 11131149