Affinage

SIGLEC1

Sialoadhesin · UniProt Q9BZZ2

Length
1709 aa
Mass
182.6 kDa
Annotated
2026-06-10
100 papers in source corpus 27 papers cited in narrative 27 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

SIGLEC1 (CD169/sialoadhesin) is a macrophage- and dendritic cell-restricted sialic acid-binding I-type lectin that functions as an endocytic pattern-recognition receptor coupling sialylated-ligand capture to immune surveillance, antigen handling, and modulation of innate immune signaling (PMID:23271952, PMID:26358190). Through its sialic acid-binding site it recognizes α2,3-linked sialic acids and sialyllactose-containing gangliosides (GM3), with the N-acyl side chain of sialic acid acting as a key specificity determinant, enabling glycoprotein-independent capture of enveloped viruses, exosomes, and sialylated counterreceptors such as CD43 on T cells (PMID:11238599, PMID:26370074, PMID:24947940). CD169 captures HIV-1, MLV, Ebola, and SARS-CoV-2 via ganglioside recognition and traffics cargo into non-lysosomal virus-containing compartments (VCCs) that shield virions from neutralizing antibodies and are delivered to lymphocytes for trans-infection (PMID:23593001, PMID:26429886, PMID:31160823, PMID:25760631); ganglioside engagement drives Rho-ROCK- and formin-actin-dependent nanoclustering that concentrates particles into a single sac-like VCC, and the receptor also localizes to tunneling nanotubes to mediate cell-to-cell viral transfer (PMID:36940134, PMID:32223897). Beyond pathogen capture, CD169 transduces intracellular signals through DAP12: it recruits SHP2 and the E3 ligase TRIM27 to drive K48-linked ubiquitination and degradation of TBK1, suppressing type I IFN, while a DAP12/Syk arm promotes TGF-β1 production in tolerant macrophages (PMID:26358190, PMID:27129263). Because SIGLEC1 is transcriptionally induced by the IFN/JAK/STAT1 axis, this establishes a negative-feedback circuit on antiviral immunity (PMID:26358190). CD169+ macrophages also mediate antigen transfer to cross-priming CD8α+ dendritic cells and uptake of bacterial extracellular vesicles, and their differentiation in lymphoid organs requires dual RANK and LTβR signaling (PMID:29425504, PMID:33489013, PMID:35031565). A SIGLEC1 null variant (Glu88Ter) is associated with extrapulmonary dissemination of Mycobacterium tuberculosis (PMID:33489013).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2001 High

    Establishing what natural ligands sialoadhesin engages was needed to define its receptor function; identification of T cell CD43/PSGL-1 as sialic acid-dependent counterreceptors gave it a defined cellular target.

    Evidence Sialoadhesin-Fc pulldown with active-site (R97A) mutagenesis and COS cell expression

    PMID:11238599

    Open questions at the time
    • Functional consequence of CD43 engagement for T cells not established here
    • Did not address viral or vesicle ligands
  2. 2011 High

    Whether CD169 is an internalizing receptor and where cargo is delivered was unclear; demonstrating clathrin/Eps15-dependent endocytosis to early endosomes but not lysosomes defined it as an endocytic receptor sparing cargo from degradation.

    Evidence Clathrin inhibitors, dominant-negative Eps15, immunofluorescence and immunotoxin in porcine macrophages

    PMID:21359217

    Open questions at the time
    • Studied in porcine system
    • Did not connect endocytic route to viral trans-infection
  3. 2012 High

    The molecular basis of DC-mediated HIV-1 trans-infection was unresolved; showing Siglec-1 binds HIV-1 and GM3-bearing vesicles glycoprotein-independently and is essential for trans-infection defined a ganglioside-recognition capture pathway distinct from DC-SIGN.

    Evidence Siglec-1 knockdown, ganglioside-vesicle binding, and trans-infection assays in mature DCs

    PMID:23271952

    Open questions at the time
    • Intracellular trafficking route not yet defined
    • Signaling consequences of capture not addressed
  4. 2013 High

    Whether GM3 recognition was sufficient and where captured virus is stored was unknown; rescue and reconstitution showed GM3-CD169 binding alone sequesters HIV-1 into non-lysosomal tetraspanin-positive compartments that traffic to the infectious synapse.

    Evidence siRNA/rescue, GSL depletion, artificial virus nanoparticle reconstitution, co-localization microscopy (multiple studies)

    PMID:23593001 PMID:24947940

    Open questions at the time
    • Cytoskeletal machinery forming the compartment not yet identified
    • In vivo relevance not established here
  5. 2013 High

    The physiological role of CD169 in lymphoid organs was unclear; showing it captures B cell-derived exosomes via α2,3-sialic acids and shapes antigen distribution extended its function to endogenous sialylated vesicles.

    Evidence CD169−/− mice, tissue-section binding assays, exosome distribution analysis

    PMID:24255917

    Open questions at the time
    • Downstream antigen-presentation pathway not detailed
    • Signaling not addressed
  6. 2015 High

    How CD169 modulates innate signaling was unknown; identifying the DAP12/SHP2/TRIM27 axis that ubiquitinates and degrades TBK1, together with IFN/STAT1 induction of SIGLEC1, defined a negative-feedback brake on type I IFN.

    Evidence Co-IP, ubiquitination assays, TBK1 K251/K372 mutagenesis, knockdown/overexpression

    PMID:26358190

    Open questions at the time
    • In vivo significance of IFN suppression incompletely defined here
    • Ligand triggering the signal not specified
  7. 2015 High

    Whether trans-infection occurs in vivo and the chemical determinants of capture were open; intravital imaging in CD169 KO mice and systematic sialic acid N-acyl engineering established in vivo synaptic trans-infection and the N-acyl side chain as a specificity determinant.

    Evidence Intravital microscopy, CD169 KO mice, MLV/HIV models, biosynthetic sialic acid analogs and modeling

    PMID:26370074 PMID:26429886

    Open questions at the time
    • Quantitative contribution relative to other capture routes unclear
    • Human in vivo data lacking
  8. 2015 High

    How the protective virus-containing compartment forms and what determines retention was unknown; cytoplasmic-tail mutagenesis and VCC quantification showed CD169 initiates VCC formation, the cytoplasmic tail is dispensable for retention, and VCCs shield virus from broadly neutralizing antibodies.

    Evidence Super-resolution microscopy, CD169 cytoplasmic-tail mutagenesis, bNAb neutralization and VCC formation assays

    PMID:25760631 PMID:28129379

    Open questions at the time
    • Actin/Rho machinery driving compartment formation not yet identified
    • Endocytic motif effect mechanistically unresolved
  9. 2015 High

    Whether the lectin function is conserved and broadly co-opted by viruses was unclear; showing porcine, murine, and human Siglec-1 each promote PRRSV infection in a sialic acid-binding-dependent manner via active-site mutants generalized the capture mechanism across orthologs and pathogens.

    Evidence Recombinant species-specific Siglec-1 and binding-site mutants in CD163+ cells, PRRSV infection

    PMID:23740482

    Open questions at the time
    • Did not address trafficking in this context
    • Trans-infection not tested
  10. 2016 High

    Whether CD169 signals beyond IFN suppression was unknown; identifying a DAP12/Syk arm that promotes TGF-β1 in endotoxin-tolerant macrophages broadened its signaling output toward immune tolerance.

    Evidence Co-IP of Siglec-1/DAP12/Syk, siRNA, Syk inhibitor, ubiquitination and tolerance assays in RAW264.7

    PMID:27129263

    Open questions at the time
    • Ligand initiating tolerant-macrophage signaling not defined
    • In vivo relevance not tested
  11. 2016 High

    What controls CD169+ macrophage development in lymphoid organs was unknown; conditional RANK and LTβR ablation with a RANKL reporter showed dual signaling is required for differentiation and downstream viral capture and CD8+ T cell expansion.

    Evidence Conditional RANK/LTβR knockout, RANKL reporter mouse, viral capture and T cell assays

    PMID:35031565

    Open questions at the time
    • Transcriptional program downstream of RANK/LTβR not detailed
    • Human relevance not addressed
  12. 2018 High

    Whether CD169 contributes to adaptive priming was open; sialic acid-binding mutants and BATF3 KO showed CD169 mediates antigen transfer to cross-priming CD8α+ DCs, linking lectin capture to CD8 T cell activation.

    Evidence CD169 blocking/binding mutants, BATF3 KO, DNGR-1 blocking, in vivo MVA model

    PMID:29425504

    Open questions at the time
    • Molecular form of transferred antigen not defined
    • Signaling in macrophage during transfer unclear
  13. 2019 High

    The breadth of viral substrates and translational potential of blockade were unclear; anti-Siglec-1 antibodies blocking Ebola uptake with cross-protection against HIV-1, plus pre-DC and cervical DC capture data, generalized CD169 as a pan-enveloped-virus capture receptor and therapeutic target.

    Evidence Anti-Siglec-1 mAb blockade, viral uptake/fusion assays, pre-DC infection and ex vivo cervical DC models

    PMID:31114569 PMID:31160823 PMID:31591213

    Open questions at the time
    • In vivo efficacy of blockade not established
    • Cervical DC data single-lab, medium confidence
  14. 2019 Medium

    Whether CD169 acts in cancer was unknown; sinus-lining macrophage CD169 anchoring hypersialylated melanoma cells and driving proliferation, with St3gal3 KO compromising metastasis, extended the lectin role to lymph node metastatic niches.

    Evidence Co-culture, transcriptomics, St3gal3 KO, GFP-melanoma implantation

    PMID:31872800

    Open questions at the time
    • Single lab
    • Direct CD169-ligand on tumor cells not molecularly resolved
  15. 2020 High

    How captured virus moves between cells beyond synapses was unclear; showing IFN-I-dependent Siglec-1 enrichment on tunneling nanotubes that mediate HIV transfer, exacerbated in TB co-infection, added a cytoskeletal conduit to its trafficking repertoire.

    Evidence siRNA depletion, TNT length measurement, HIV capture/transfer assays, NHP co-infection model

    PMID:32223897

    Open questions at the time
    • Molecular link between Siglec-1 and TNT formation incomplete
    • Generalizability to other viruses untested here
  16. 2021 Medium

    Whether SIGLEC1 has a protective antibacterial role and a human genetic phenotype was unknown; KO mice and a Glu88Ter null variant linked CD169-dependent EV uptake to control of early Mtb dissemination.

    Evidence SIGLEC1 null-variant genotyping, KO mouse Mtb infection, EV uptake/antigen presentation assays

    PMID:33489013

    Open questions at the time
    • Single lab
    • Causality of Glu88Ter variant not functionally proven
    • Mechanism of EV-driven protection partial
  17. 2022 High

    Whether CD169 supports a productive or abortive viral fate was unresolved for SARS-CoV-2; showing ACE2-independent fusion/entry with a post-entry replication block triggering RIG-I/MDA-5/MAVS inflammation revealed CD169 entry can drive inflammation without productive infection.

    Evidence CD169 blocking, exogenous ACE2 rescue, viral RNA quantification, RIG-I/MDA-5/MAVS KO, remdesivir

    PMID:36279285

    Open questions at the time
    • In vivo contribution to COVID-19 inflammation not established
    • Determinant of the replication block undefined
  18. 2023 High

    The biophysical mechanism forming the single VCC was unknown; super-resolution and single-particle tracking with Rho-ROCK and formin perturbations showed ganglioside binding triggers Siglec-1 nanoclustering and actin rearrangement to concentrate virions into one sac-like compartment.

    Evidence STORM/PALM, single-particle tracking, ROCK/formin inhibitors, RhoA activity assays, ganglioside liposomes

    PMID:36940134

    Open questions at the time
    • Link between nanoclustering and DAP12 signaling not connected
    • Whether mechanism applies to non-viral cargo untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ligand engagement is mechanistically partitioned between endocytic/trans-infection trafficking and the DAP12/SHP2 and DAP12/Syk signaling outputs, and how these are integrated in vivo, remains unresolved.
  • No unified model linking nanoclustering, VCC formation, and DAP12 signaling
  • Ligand-specific signaling outcomes undefined
  • Therapeutic blockade efficacy in vivo unestablished

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0001618 virus receptor activity 6 GO:0038024 cargo receptor activity 4 GO:0060089 molecular transducer activity 2 GO:0098631 cell adhesion mediator activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005856 cytoskeleton 2 GO:0031410 cytoplasmic vesicle 2 GO:0005768 endosome 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 3 R-HSA-162582 Signal Transduction 2 R-HSA-5653656 Vesicle-mediated transport 2
Partners
CD43DAP12PSGL-1SHP2SYKTRIM27

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 CD43 (and CD162/PSGL-1) was identified as a T cell counterreceptor for sialoadhesin (Siglec-1). Sialoadhesin-Fc fusion proteins precipitated CD43 and PSGL-1 from T cell lines in a sialic acid-dependent manner; mutation of R97A in the sialic acid-binding site of sialoadhesin abolished binding. CD43 expressed in COS cells supported increased binding to immobilized sialoadhesin. Sialoadhesin-Fc pulldown, active-site mutagenesis (R97A), COS cell expression, CHO cell glycoform analysis Journal of immunology High 11238599
2012 Siglec-1 (CD169) on mature dendritic cells specifically binds HIV-1 and vesicles carrying sialyllactose-containing gangliosides (GM3) in a glycoprotein-independent manner, and is essential for DC-mediated trans-infection of CD4+ T cells. This identifies a ganglioside-recognition pathway distinct from DC-SIGN. Siglec-1 expression on mature DCs, binding assays with HIV-1 and ganglioside-containing vesicles, siRNA knockdown of Siglec-1, trans-infection assays PLoS biology High 23271952
2013 Siglec-1/CD169 is required for capture of B cell-derived exosomes in spleen (marginal zone) and lymph node (subcapsular sinus) via recognition of α2,3-linked sialic acids on exosome surfaces. CD169−/− mice showed altered exosome distribution and enhanced immune responses to exosomal antigen. In vitro binding assays on lymphoid tissue sections, CD169−/− knockout mice, flow cytometry-based exosome distribution analysis Blood High 24255917
2013 IFNα-activated Siglec-1/CD169 on DCs captures HIV-1 in a GM3 ganglioside-dependent manner; selective CD169 downregulation or GSL depletion from virions abolished DC-mediated HIV capture and trans-infection; exogenous CD169 expression in naive cells rescued GSL-dependent capture. HIV-1 particles co-localized with CD169 at the DC surface and within non-lysosomal compartments that redistributed to DC–T cell infectious synapses. siRNA knockdown, exogenous CD169 expression rescue, GSL depletion from virions, co-localization microscopy, trans-infection functional assay PLoS pathogens High 23593001
2015 Siglec-1 associates with DAP12 to recruit and activate SHP2; SHP2 then recruits E3 ubiquitin ligase TRIM27, which induces K48-linked ubiquitination and degradation of TBK1 at Lys251 and Lys372, thereby suppressing viral infection-triggered type I IFN production in macrophages. Expression of Siglec-1 is induced by the IFN/JAK/STAT1 pathway during viral infection, creating a negative feedback loop. Co-immunoprecipitation, ubiquitination assays, mutagenesis of TBK1 ubiquitination sites (K251, K372), siRNA knockdown, overexpression studies Cell research High 26358190
2015 CD169/Siglec-1 on sinus-lining macrophages captures murine leukemia virus (MLV) and HIV via ganglioside recognition; MLV-laden macrophages form long-lived synaptic contacts with B-1 cells to mediate trans-infection; CD169 was required for robust infection in lymph nodes and spleen in vivo. Intravital microscopy in living mice, CD169 knockout mice, retroviral infection models (MLV and HIV) Science High 26429886
2015 Siglec-1 mediates trans-infection of surface-bound murine leukemia virus (MLV) to B cells in a sialic acid N-acyl side chain-dependent manner. The N-acyl modification of sialic acid in viral membrane gangliosides is a critical determinant for Siglec-1/MLV interaction; N-butanoyl, N-isobutanoyl, N-glycolyl, and N-pentanoyl modifications reduced capture by up to 92%. Primary macrophage trans-infection assay, biosynthetic sialic acid analog engineering, molecular modeling, co-localization of Gag with Siglec-1 Journal of biological chemistry High 26370074
2015 Siglec-1 on macrophages initiates formation of the virus-containing compartment (VCC) by capturing ganglioside-bearing viral particles from the extracellular space. Siglec-1 depletion or ganglioside depletion from particles prevented VCC formation and reduced Siglec-1-mediated trans-infection of autologous T cells. Siglec-1 knockdown in macrophages, exogenous addition of VLPs and virions, ganglioside depletion, VCC volume quantification, trans-infection assay PLoS pathogens High 28129379
2015 CD169-mediated trafficking of HIV-1 into plasma membrane invaginations (VCCs) in dendritic cells protects virus from neutralization by broadly neutralizing anti-gp120 antibodies (VRC01, NIH45-46 G54W). The cytoplasmic tail of CD169 is dispensable for HIV-1 trafficking and retention within VCCs, but introduction of a di-aromatic endocytic motif into the cytoplasmic tail suppressed trans-infection. Super-resolution microscopy, cytoplasmic tail mutagenesis of CD169, neutralization assays with bNAbs, VCC formation assays PLoS pathogens High 25760631
2014 GM3-CD169 interaction drives gp120-independent HIV-1 sequestration into non-lysosomal tetraspanin-positive compartments in dendritic cells. Artificial virus nanoparticles (AVNs) containing GM3 in a defined membrane composition recapitulated CD169-dependent HIV-1 uptake and compartment sequestration. Artificial virus nanoparticle reconstitution, CD169-expressing HeLa cells and mature DCs, co-localization microscopy, liposome binding Nature communications High 24947940
2011 Porcine sialoadhesin (CD169) functions as an endocytic receptor; antibody-triggered internalization is clathrin- and Eps15-dependent and delivers cargo to early endosomes but not lysosomes. Demonstrated in primary porcine macrophages and cells expressing recombinant porcine sialoadhesin using chemical inhibitors, double immunofluorescence, and dominant-negative constructs. Clathrin pathway inhibitors, dominant-negative Eps15 constructs, double immunofluorescence, immunotoxin conjugates PloS one High 21359217
2016 Siglec-1 promotes TGF-β1 production in endotoxin-tolerant macrophages by associating with adaptor protein DAP12 and transducing a signal to Syk kinase. Siglec-1 knockdown in RAW264.7 cells inhibited TGF-β1 production via ubiquitin-dependent degradation of Syk; this was attenuated by Syk inhibitor. Co-immunoprecipitation of Siglec-1 and DAP12/Syk, siRNA knockdown, Syk inhibitor, ubiquitination assay, TNF-α tolerance assay Journal of biological chemistry High 27129263
2015 miR-27a directly targets Siglec-1 (and TRIM27); IFN/JAK/STAT1/RUNX1-mediated downregulation of miR-27a during viral infection de-represses Siglec-1 and TRIM27, inhibiting type I IFN production. In miR-27a-sponge transgenic mice, Siglec-1 and TRIM27 were elevated and type I IFN production was inhibited in vivo. miR-27a sponge transgenic mice, luciferase reporter assays for miR-27a targeting of Siglec-1, qPCR, VSV infection model Journal of immunology Medium 26700765
2018 CD169 sialic acid-binding capacity is required for antigen transfer from CD169+ macrophages to BATF3-dependent CD8α+ dendritic cells (DCs) in the spleen, enabling cross-priming of CD8+ T cells. CD169 preferentially binds CD8α+ DCs and the sialic acid-binding function mediates the macrophage–DC interaction. CD169 blocking antibodies and sialic acid-binding mutants, DC subset depletion (BATF3 KO), DNGR-1 blocking, in vivo antigen targeting, modified vaccinia Ankara infection model Cell reports High 29425504
2019 Siglec-1 recognizes sialylated gangliosides on Ebola virus membranes, mediating viral uptake into activated dendritic cells; blockade with anti-Siglec-1 monoclonal antibodies halted Ebola virus uptake and cytoplasmic entry, and provided cross-protection against HIV-1. Anti-Siglec-1 monoclonal antibody blockade, viral uptake assays in activated DCs, cytoplasmic entry quantification, cross-virus comparison Nature microbiology High 31160823
2019 Siglec-1-expressing subcapsular sinus macrophages provide anchorage to hypersialylated pioneer metastatic melanoma cells, and Siglec-1 interaction drives proliferation of cancer cells. Knockout of St3gal3 sialyltransferase in tumor cells reduced α2,3-linked sialylation and compromised metastatic efficiency in lymph nodes. In vitro co-culture of cancer cells with Siglec-1+ macrophages, transcriptome profiling, St3gal3 knockout, GFP-melanoma implantation model eLife Medium 31872800
2020 Siglec-1 on macrophages localizes predominantly to microtubule-containing tunneling nanotubes (TNTs) in a TB-associated IFN-I-dependent manner. Siglec-1 depletion decreases TNT length, diminishes HIV-1 capture and cell-to-cell transfer via TNTs, and abrogates TB-induced exacerbation of HIV-1 infection. Siglec-1 siRNA depletion, transcriptomic analysis, TNT length measurement, HIV-1 capture and transfer assays in macrophages, non-human primate co-infection model with immunohistochemistry eLife High 32223897
2022 CD169 facilitates ACE2-independent SARS-CoV-2 fusion and entry into macrophages. CD169-mediated entry results in expression of viral genomic and subgenomic RNAs with minimal viral protein and no infectious particle release (post-entry replication block), and this restricted viral RNA expression triggers RIG-I/MDA-5/MAVS-dependent pro-inflammatory cytokine production (TNFα, IL-6, IL-1β). CD169 blocking, exogenous ACE2 rescue expression, viral RNA quantification, innate immune pathway knockout (RIG-I/MDA-5/MAVS), remdesivir treatment PLoS pathogens High 36279285
2023 Siglec-1 nanoclustering at the plasma membrane of activated DCs is regulated by Rho-ROCK activation and formin-dependent actin polymerization. Ganglioside binding (HIV-1 or ganglioside liposomes) triggers enhanced Siglec-1 nanoclustering and global actin rearrangements (drop in RhoA activity) that facilitate accumulation of viral particles into a single sac-like VCC. Super-resolution microscopy (STORM/PALM), single-particle tracking, biochemical perturbations (ROCK inhibitor, formin inhibitor), liposomes with varying ganglioside concentrations, RhoA activity assays eLife High 36940134
2021 Siglec-1 is required to induce antigen presentation through uptake of extracellular vesicles (EVs) from Mycobacterium tuberculosis. A SIGLEC1 null variant (Glu88Ter) is associated with extrapulmonary dissemination of Mtb; Siglec-1 knockout mice showed more extensive lung lesions. Siglec-1 limits early local spread of mycobacteria by facilitating antigen exchange via EVs. SIGLEC1 null variant genotyping in clinical cohorts, Siglec-1 knockout mice Mtb infection model, EV uptake and antigen presentation assays Journal of extracellular vesicles Medium 33489013
2016 CD169+ macrophage differentiation in lymph nodes and spleen requires dual signaling through RANK and LTβR; loss of either receptor perturbs differentiation. Splenic marginal zone stromal cells were identified as a source of RANKL via a RANKL reporter mouse. Loss of marginal metallophilic macrophages (MMMs) compromised viral capture and CD8+ T cell expansion. Conditional receptor ablation (RANK and LTβR KO), RANKL reporter mouse, flow cytometry, viral capture assays, CD8+ T cell functional readout Proceedings of the National Academy of Sciences High 35031565
2019 Cervical DCs expressing Siglec-1 capture HIV-1 and mediate trans-infection; a type-I IFN environment enhanced viral capture and trans-infection via Siglec-1; antibodies against Siglec-1 effectively prevented HIV-1 transfer via cervical DCs. Ex vivo cervical biopsy analysis, anti-Siglec-1 antibody blockade, IFN treatment, viral capture and trans-infection assays Frontiers in immunology Medium 31114569
2016 Siglec-1 on alveolar macrophages mediates phagocytosis of non-typeable Haemophilus influenzae (NTHi); blocking Siglec-1 with an anti-Siglec-1 antibody decreased phagocytosis of NTHi by human alveolar macrophages. Siglec-1 expression was significantly decreased on alveolar macrophages in COPD patients. Anti-Siglec-1 blocking antibody in phagocytosis assay, flow cytometry of human alveolar macrophages, correlation with lung function Respiratory research Medium 31992280
2019 Pre-DC blood dendritic cell precursors constitutively express Siglec-1 and are specifically susceptible to HIV-1 infection in a Siglec-1-dependent manner (both CCR5- and CXCR4-tropic strains). Siglec-1 promotes viral attachment and fusion, and HIV-1-infected pre-DCs accumulate virus in intracellular compartments resembling the VCC. Siglec-1 remains functional in antiviral TLR-activated pre-DCs for replication-independent HIV-1 transfer to T cells. Siglec-1-dependent infection assay in pre-DCs vs. other DC subsets, Vpx restriction factor analysis, HIV-1 fusion assay, T cell trans-infection assay Proceedings of the National Academy of Sciences High 31591213
2017 IFNα-induced CD169 expression on macrophages and DCs attenuates the antiviral effects of type I IFN by enhancing HIV-1 entry in a CD169-dependent manner (cis infection) and by rescuing HIV-1 infection of CD4+ T cells in trans via DC–T cell co-culture. In SIV/RT-SHIV-infected macaques, CD169 expression was enhanced in lymph nodes and showed extensive co-localization with p27gag. CD169-dependent HIV-1 entry assay in IFNα-treated THP-1 and primary MDMs, DC–T cell co-culture trans-infection, immunohistochemistry in pigtailed macaque lymph nodes Journal of virology Medium 28794041
2018 Siglec-1 on RSV-infected adult monocytes inhibits IFN-γ production by adult CD4+ T cells, and this inhibition is mediated by Siglec-1 binding to its ligand CD43, which is highly expressed on adult but not newborn CD4+ T cells. In vitro co-culture of monocytes and T cells, anti-Siglec-1 blocking, CD43 expression analysis by flow cytometry, RSV infection model European journal of immunology Medium 29266251
2013 Porcine, murine, and human sialoadhesin (Siglec-1) can each promote PRRSV infection of CD163-expressing cells; intact sialic acid-binding domains are crucial, as non-sialic acid-binding mutants of all three species' Siglec-1 failed to promote infection. Recombinant expression of species-specific Siglec-1 and sialic acid-binding mutants in CD163+ cells, PRRSV infection assay Journal of general virology High 23740482

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 656 21282381
2010 CD169-positive macrophages dominate antitumor immunity by crosspresenting dead cell-associated antigens. Immunity 375 21194983
2013 CD169⁺ macrophages provide a niche promoting erythropoiesis under homeostasis and stress. Nature medicine 354 23502962
2013 CD169 mediates the capture of exosomes in spleen and lymph node. Blood 307 24255917
2012 Siglec-1 is a novel dendritic cell receptor that mediates HIV-1 trans-infection through recognition of viral membrane gangliosides. PLoS biology 201 23271952
2010 CD169(+) macrophages present lipid antigens to mediate early activation of iNKT cells in lymph nodes. Nature immunology 174 20228797
2011 CD169+ macrophages at the crossroads of antigen presentation. Trends in immunology 170 22192781
2015 Siglec1 suppresses antiviral innate immune response by inducing TBK1 degradation via the ubiquitin ligase TRIM27. Cell research 161 26358190
2017 CD169+ macrophages are critical for osteoblast maintenance and promote intramembranous and endochondral ossification during bone repair. Biomaterials 151 29107337
2015 Retroviruses use CD169-mediated trans-infection of permissive lymphocytes to establish infection. Science (New York, N.Y.) 145 26429886
2013 Interferon-inducible mechanism of dendritic cell-mediated HIV-1 dissemination is dependent on Siglec-1/CD169. PLoS pathogens 143 23593001
2012 IFNα and its response proteins, IP-10 and SIGLEC-1, are biomarkers of disease activity in systemic lupus erythematosus. Annals of the rheumatic diseases 119 23117242
2001 Cutting edge: CD43 functions as a T cell counterreceptor for the macrophage adhesion receptor sialoadhesin (Siglec-1). Journal of immunology (Baltimore, Md. : 1950) 112 11238599
2018 Functional CD169 on Macrophages Mediates Interaction with Dendritic Cells for CD8+ T Cell Cross-Priming. Cell reports 109 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 106 23785195
2018 CD169+ Macrophages Capture and Dendritic Cells Instruct: The Interplay of the Gatekeeper and the General of the Immune System. Frontiers in immunology 102 30416504
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 95 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
2017 CD169+ macrophages orchestrate innate immune responses by regulating bacterial localization in the spleen. Science immunology 85 28986418
2012 Subcapsular sinus macrophage fragmentation and CD169+ bleb acquisition by closely associated IL-17-committed innate-like lymphocytes. PloS one 83 22675532
2022 Blood monocyte-derived CD169+ macrophages contribute to antitumor immunity against glioblastoma. Nature communications 77 36266311
2017 Siglec-1 initiates formation of the virus-containing compartment and enhances macrophage-to-T cell transmission of HIV-1. PLoS pathogens 77 28129379
2015 HIV-1 immune activation induces Siglec-1 expression and enhances viral trans-infection in blood and tissue myeloid cells. Retrovirology 77 25947229
2011 Porcine sialoadhesin (CD169/Siglec-1) is an endocytic receptor that allows targeted delivery of toxins and antigens to macrophages. PloS one 74 21359217
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 71 33067394
2016 CD169 identifies an anti-tumour macrophage subpopulation in human hepatocellular carcinoma. The Journal of pathology 70 27174787
2016 Tissue-Resident CD169(+) Macrophages Form a Crucial Front Line against Plasmodium Infection. Cell reports 70 27477286
2007 Sialoadhesin (CD169) expression in CD14+ cells is upregulated early after HIV-1 infection and increases during disease progression. PloS one 66 17330143
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
2014 Glycosphingolipid-functionalized nanoparticles recapitulate CD169-dependent HIV-1 uptake and trafficking in dendritic cells. Nature communications 60 24947940
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) 59 24196391
2019 Breast cancer cells promote CD169+ macrophage-associated immunosuppression through JAK2-mediated PD-L1 upregulation on macrophages. International immunopharmacology 57 31865052
2021 CD169+ lymph node macrophages have protective functions in mouse breast cancer metastasis. Cell reports 56 33852863
2016 CD169+ macrophages regulate PD-L1 expression via type I interferon and thereby prevent severe immunopathology after LCMV infection. Cell death & disease 56 27809306
2021 Monocyte CD169 Expression as a Biomarker in the Early Diagnosis of Coronavirus Disease 2019. The Journal of infectious diseases 54 33206973
2021 CD169 Defines Activated CD14+ Monocytes With Enhanced CD8+ T Cell Activation Capacity. Frontiers in immunology 54 34394090
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 52 25487358
2019 Anti-Siglec-1 antibodies block Ebola viral uptake and decrease cytoplasmic viral entry. Nature microbiology 49 31160823
2016 SIGLEC1 is a biomarker of disease activity and indicates extraglandular manifestation in primary Sjögren's syndrome. RMD open 48 28123773
2014 The identification and developmental requirements of colonic CD169⁺ macrophages. Immunology 47 24883436
2022 Siglec-1 expression on monocytes is associated with the interferon signature in juvenile dermatomyositis and can predict treatment response. Rheumatology (Oxford, England) 46 34387304
2018 Targeted Delivery of Antigen to Activated CD169+ Macrophages Induces Bias for Expansion of CD8+ T Cells. Cell chemical biology 46 30393066
2017 Interferon-Inducible CD169/Siglec1 Attenuates Anti-HIV-1 Effects of Alpha Interferon. Journal of virology 44 28794041
2022 CD169-mediated restrictive SARS-CoV-2 infection of macrophages induces pro-inflammatory responses. PLoS pathogens 43 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 43 32031762
2019 Dendritic Cells From the Cervical Mucosa Capture and Transfer HIV-1 via Siglec-1. Frontiers in immunology 42 31114569
2018 Siglec-1 Macrophages and the Contribution of IFN to the Development of Autoimmune Congenital Heart Block. Journal of immunology (Baltimore, Md. : 1950) 41 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 41 28501799
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
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 40 31591213
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 38 34563673
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
2015 Type I IFN-Inducible Downregulation of MicroRNA-27a Feedback Inhibits Antiviral Innate Response by Upregulating Siglec1/TRIM27. Journal of immunology (Baltimore, Md. : 1950) 38 26700765
2019 Siglec1-expressing subcapsular sinus macrophages provide soil for melanoma lymph node metastasis. eLife 37 31872800
2015 The CD169 sialoadhesin molecule mediates cytotoxic T-cell responses to tumour apoptotic vesicles. Immunology and cell biology 37 26647968
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 34 35044489
2022 Myeloid CD169/Siglec1: An immunoregulatory biomarker in viral disease. Frontiers in medicine 34 36213653
2017 CD169 is a marker for highly pathogenic phagocytes in multiple sclerosis. Multiple sclerosis (Houndmills, Basingstoke, England) 34 28277099
2014 CD169-dependent cell-associated HIV-1 transmission: a driver of virus dissemination. The Journal of infectious diseases 34 25414418
2022 SIGLEC1 enables straightforward assessment of type I interferon activity in idiopathic inflammatory myopathies. RMD open 32 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 31 26370074
2009 Siglec-1 on monocytes is a potential risk marker for monitoring disease severity in coronary artery disease. Clinical biochemistry 31 19285973
2021 Liposomal Nanovaccine Containing α-Galactosylceramide and Ganglioside GM3 Stimulates Robust CD8+ T Cell Responses via CD169+ Macrophages and cDC1. Vaccines 30 33467048
2021 The role of sialic acid-binding immunoglobulin-like-lectin-1 (siglec-1) in immunology and infectious disease. International reviews of immunology 29 34494938
2020 SIGLEC1 (CD169) is a sensitive biomarker for the deterioration of the clinical course in childhood systemic lupus erythematosus. Lupus 29 33081587
2018 A Protective Role for the Lectin CD169/Siglec-1 against a Pathogenic Murine Retrovirus. Cell host & microbe 29 30595553
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
2018 Siglec-1 inhibits RSV-induced interferon gamma production by adult T cells in contrast to newborn T cells. European journal of immunology 28 29266251
2016 Identification of Siglec-1 null individuals infected with HIV-1. Nature communications 27 27510803
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 26 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 26 33493613
2020 Decreased expression of a phagocytic receptor Siglec-1 on alveolar macrophages in chronic obstructive pulmonary disease. Respiratory research 26 31992280
2023 Breast cancer associated CD169+ macrophages possess broad immunosuppressive functions but enhance antibody secretion by activated B cells. Frontiers in immunology 25 37404831
2020 Optimization of Liposomes for Antigen Targeting to Splenic CD169+ Macrophages. Pharmaceutics 25 33255564
2019 Low Dose of Cyanidin-3-O-Glucoside Alleviated Dextran Sulfate Sodium-Induced Colitis, Mediated by CD169+ Macrophage Pathway. Inflammatory bowel diseases 25 31107535
2019 When Dendritic Cells Go Viral: The Role of Siglec-1 in Host Defense and Dissemination of Enveloped Viruses. Viruses 24 31861617
2018 Preferential use of Siglec-1 or Siglec-10 by type 1 and type 2 PRRSV strains to infect PK15S1-CD163 and PK15S10-CD163 cells. Veterinary research 24 30021620
2021 SIGLEC1 (CD169): a marker of active neuroinflammation in the brain but not in the blood of multiple sclerosis patients. Scientific reports 23 33986412
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
2023 CD169 expression on monocytes as a marker for assessing type I interferon status in pediatric inflammatory diseases. Clinical immunology (Orlando, Fla.) 21 37061149
2018 Comparison of Protein and Peptide Targeting for the Development of a CD169-Based Vaccination Strategy Against Melanoma. Frontiers in immunology 21 30237798
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 19 33869256
2020 MiR-195-5p inhibits the development of chronic obstructive pulmonary disease via targeting siglec1. Human & experimental toxicology 19 32351126
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
2012 SIGLEC1 and SIGLEC7 expression in circulating monocytes of patients with multiple sclerosis. Multiple sclerosis (Houndmills, Basingstoke, England) 19 22933622
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
2015 Effect of cytokines on Siglec-1 and HIV-1 entry in monocyte-derived macrophages: the importance of HIV-1 envelope V1V2 region. Journal of leukocyte biology 18 26667473
2022 SIGLEC-1 in Systemic Sclerosis: A Useful Biomarker for Differential Diagnosis. Pharmaceuticals (Basel, Switzerland) 17 36297311
2016 Siglec-1 and -2 as potential biomarkers in autoimmune disease. Proteomics. Clinical applications 17 26752092
2013 Porcine, murine and human sialoadhesin (Sn/Siglec-1/CD169): portals for porcine reproductive and respiratory syndrome virus entry into target cells. The Journal of general virology 17 23740482
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
2023 Actin-regulated Siglec-1 nanoclustering influences HIV-1 capture and virus-containing compartment formation in dendritic cells. eLife 16 36940134
2022 Evaluation of SIGLEC1 in the diagnosis of suspected systemic lupus erythematosus. Rheumatology (Oxford, England) 16 34849605
2021 Dissemination of Mycobacterium tuberculosis is associated to a SIGLEC1 null variant that limits antigen exchange via trafficking extracellular vesicles. Journal of extracellular vesicles 16 33489013
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

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