Affinage

TLR6

Toll-like receptor 6 · UniProt Q9Y2C9

Length
796 aa
Mass
91.9 kDa
Annotated
2026-06-10
100 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TLR6 is a type-I transmembrane pattern-recognition receptor with an extracellular leucine-rich repeat domain and a cytoplasmic TIR domain that drives NF-κB and JNK signaling (PMID:10231569). Its principal mode of action is as a co-receptor: by heterodimerizing with TLR2 it expands the recognized ligand spectrum to diacylated bacterial and mycoplasmal lipopeptides, peptidoglycan, and diverse microbial products, while the partner TLR1 forms an opposing TLR2 heterodimer with distinct ligand specificity (PMID:11123271, PMID:15661917, PMID:18056480). TLR2/TLR6 dimerization recruits the adaptors MyD88 and TIRAP/Mal to activate NF-κB and the p38/JNK MAPK cascades, and depends on agonist-induced tyrosine phosphorylation of TLR2 — a step impaired by the TLR2 R753Q polymorphism, which abrogates TLR6 heterodimerization and adaptor recruitment (PMID:17202370, PMID:22992740). A high-resolution TIR-domain crystal structure defines a homo-dimerization interface required for engaging TIR-containing adaptors (PMID:25088687). Functional outcomes of TLR2/TLR6 signaling are context-dependent, spanning proinflammatory cytokine production, MyD88/FADD/p38-dependent apoptosis (PMID:14706104), IL-23-driven Th17 responses in dendritic cells (PMID:22005301), lipid-droplet biogenesis favoring intracellular bacterial persistence (PMID:21813774), and hematopoietic recovery after radiation injury (PMID:38051771). TLR6 also pairs with TLR4 at the plasma membrane in response to amyloid-β to drive microglial inflammation (PMID:28655763). TLR6 expression is transcriptionally induced during hypoxia through direct HIF-1α binding to its promoter (PMID:18159247), and TLR6/JNK signaling is desensitized during persistent H. pylori infection to establish immune tolerance (PMID:38310631).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1999 Medium

    Established that TLR6 is a TIR-domain transmembrane receptor capable of activating innate immune signaling, defining it as a candidate pattern-recognition receptor.

    Evidence Molecular cloning and constitutively active construct transfection with NF-κB and JNK reporter assays

    PMID:10231569

    Open questions at the time
    • No natural ligand identified
    • Activity shown only with a forced constitutively active construct, not native receptor
  2. 2001 High

    Showed TLR6 acts as a functional partner of TLR2 (and is opposed by TLR1), reframing it from a standalone receptor to a co-receptor that tunes TLR2 responses.

    Evidence Gain-of-function co-expression of TLR constructs with NF-κB activation assays in reporter cells

    PMID:11123271

    Open questions at the time
    • Physical heterodimerization not demonstrated biochemically
    • Molecular basis of TLR1 vs TLR6 ligand discrimination unresolved
  3. 2004 High

    Defined the downstream adaptor and effector chain of TLR2/TLR6, establishing that the dimer can drive apoptosis as well as NF-κB activation.

    Evidence Co-transfection with dominant-negative MyD88/FADD/IRAK-4, caspase-8 activation assay, and p38 inhibitor in HEK293 cells

    PMID:14706104

    Open questions at the time
    • Reliance on overexpression and dominant-negatives rather than endogenous signaling
    • What dictates apoptotic vs proinflammatory outcome not defined
  4. 2005 High

    Localized TLR6 to the surface of myeloid cells co-clustered with TLR2 and showed signaling occurs at the plasma membrane, establishing where and in which cells the receptor operates.

    Evidence Function-blocking anti-TLR6 mAb, flow cytometry, confocal colocalization, and TLR2 Cys-mutant analysis

    PMID:15661917

    Open questions at the time
    • Stoichiometry and kinetics of TLR2/TLR6 surface assembly not resolved
    • Receptor trafficking after ligation not characterized
  5. 2006 High

    Demonstrated that TLR1 and TLR6 heterodimers diversify ligand recognition without diverging in downstream signaling, clarifying that specificity is set at the ectodomain not the effector level.

    Evidence Dominant-negative signaling constructs, MAPK immunoblotting, and microarray expression profiling with synthetic lipopeptides

    PMID:18056480

    Open questions at the time
    • Context-specific divergent outcomes seen in later studies not explained by this model
    • Structural basis of ligand discrimination not addressed
  6. 2007 High

    Genetically confirmed the obligate adaptor requirements (MyD88, TIRAP/Mal) and TLR2-TLR6 dependence for sensing a defined pathogen, moving beyond overexpression to knockout validation.

    Evidence Panel of TLR and adaptor knockout macrophages with in vitro cytokine and in vivo migration readouts for Wolbachia

    PMID:17202370

    Open questions at the time
    • Direct TLR6 ligand within the endosymbiont not identified
    • Relative contribution of TLR6 vs TLR2 not separated
  7. 2007 High

    Identified transcriptional control of TLR6, showing HIF-1α directly induces its expression under hypoxia and linking innate sensing capacity to the oxygen microenvironment.

    Evidence ChIP, promoter analysis, and conditional HIF-1α gain/loss-of-function mouse models with RT-PCR

    PMID:18159247

    Open questions at the time
    • Functional consequence of hypoxia-induced TLR6 on downstream immunity not quantified
    • Other transcriptional regulators of TLR6 not mapped
  8. 2008 Medium

    Showed TLR6 can redirect TLR1/TLR2 outputs from apoptosis toward NF-κB/cytokine production in trophoblasts, establishing it as a contextual modulator of dimer outcome.

    Evidence Antibody blocking, NF-κB assay, and cytokine ELISA in primary human first-trimester trophoblasts

    PMID:18424724

    Open questions at the time
    • Antibody-blocking only, no genetic confirmation
    • Molecular switch redirecting apoptosis vs NF-κB undefined
  9. 2011 High

    Separated a TLR6-specific function from TLR2, showing TLR6 alone drives lipid-droplet biogenesis and bacterial uptake that favors pathogen persistence.

    Evidence TLR6 knockout Schwann cells, fatty-acid synthase inhibitor, cytokine ELISA, and confocal imaging of M. leprae patient nerve tissue

    PMID:21813774

    Open questions at the time
    • Signaling route linking TLR6 to lipid-droplet machinery not delineated
    • Whether this requires TLR2 partnership unresolved
  10. 2011 High

    Established TLR6 as required for IL-23 production and Th17 polarization, connecting the receptor to adaptive immune outcomes in fungal asthma.

    Evidence Tlr6-/- mouse asthma models, in vitro DC stimulation, and exogenous IL-23 rescue

    PMID:22005301

    Open questions at the time
    • Direct TLR6 ligand driving IL-23 not identified
    • Mechanism linking TLR6 to dectin-1 expression unknown
  11. 2012 High

    Provided the biochemical mechanism of heterodimer assembly, showing TLR2 tyrosine phosphorylation gates TLR6 recruitment and adaptor docking, with a disease-associated polymorphism abolishing it.

    Evidence WT vs R753Q TLR2 transfection, co-IP for TLR2/TLR6 dimerization, phosphotyrosine immunoblotting, molecular modeling, and NF-κB reporter assay

    PMID:22992740

    Open questions at the time
    • Kinase responsible for TLR2 phosphorylation not identified
    • TLR6-side residues required for dimerization not mutationally tested here
  12. 2014 High

    Provided structural insight into the TLR6 TIR domain, defining a homo-dimerization interface needed for adaptor engagement.

    Evidence X-ray crystallography at 2.2 Å and comparative structural analysis

    PMID:25088687

    Open questions at the time
    • Functional role of the interface inferred from structure, not validated by mutagenesis
    • No structure of the full-length receptor or TLR2/TLR6 complex
  13. 2015 Medium

    Extended ligand repertoire to pore-forming toxins and viral/bacterial products and showed selective signaling biases, demonstrating ligand-tuned outputs through TLR2/TLR6.

    Evidence shRNA knockdowns, co-IP of TLR2 dimers, p38/ATF2 and NF-κB/JNK assays, and reconstituted oligomeric toxin ligands across Leishmania, Vibrio cytolysin, and Dengue NS1 systems

    PMID:25194056 PMID:25431887 PMID:26226614

    Open questions at the time
    • Direct receptor binding for several ligands not demonstrated
    • The Dengue NS1 claim was later contradicted
  14. 2017 Medium

    Identified a non-TLR2 partner, showing TLR6 pairs with TLR4 in response to amyloid-β to drive neuroinflammation, broadening TLR6's dimerization repertoire.

    Evidence Transmembrane-peptide interference, co-IP, microglial proinflammatory assays, and neuronal death rescue

    PMID:28655763

    Open questions at the time
    • Single-lab finding without genetic confirmation
    • Adaptor usage by the TLR4/TLR6 dimer not defined
  15. 2017 High

    Corrected a prior ligand assignment, showing properly folded eukaryotic Dengue NS1 signals through TLR4 rather than TLR2/TLR6 and that the earlier TLR2/6 claim arose from contaminated E. coli protein.

    Evidence TLR4/TLR2/TLR6 knockout macrophages and blocking antibodies comparing eukaryotic vs E. coli-derived NS1

    PMID:28220810

    Open questions at the time
    • Highlights that recombinant-protein ligand assignments require endotoxin/folding controls
    • Does not exclude TLR2/6 roles for other viral proteins
  16. 2023 Medium

    Established a regenerative role, showing TLR6 is required for MyD88-dependent hematopoietic recovery and that an FSL-1 agonist promotes progenitor proliferation across species.

    Evidence FSL-1 administration in irradiated mice and nonhuman primates with bone marrow cytology and hematopoietic recovery assays

    PMID:38051771

    Open questions at the time
    • Direct cellular target of TLR2/TLR6 in hematopoiesis not pinpointed
    • Single-lab study
  17. 2024 Medium

    Demonstrated dynamic regulation of TLR6 responsiveness, showing persistent H. pylori desensitizes TLR6/JNK signaling to enforce immune tolerance, reversible by restoring TLR6.

    Evidence Sustained H. pylori exposure in GES-1 cells and Mongolian gerbils with TLR6 overexpression rescue, cytokine measurement, and colonization assays

    PMID:38310631

    Open questions at the time
    • Mechanism reducing TLR6 sensitivity not defined
    • Single-lab study

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TLR6 ectodomain residues discriminate diacylated ligands and how a single TLR2/TLR6 dimer is steered toward divergent outcomes (NF-κB, apoptosis, IL-23, lipid droplets) remain unresolved.
  • No structure of the assembled TLR2/TLR6 ectodomain-ligand complex in the corpus
  • Molecular switch determining output specificity unknown
  • Kinase phosphorylating TLR2 to license dimerization unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0008289 lipid binding 3 GO:0001618 virus receptor activity 1
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3
Partners
FADDMYD88TIRAPTLR1TLR2TLR4
Complex memberships
TLR2/TLR6 heterodimerTLR4/TLR6 heterodimer

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 TLR6 is a type-I transmembrane receptor containing an extracellular leucine-rich repeat (LRR) domain and a cytoplasmic TIR domain; constitutively active TLR6 activates both NF-κB and JNK signaling pathways. Molecular cloning, constitutively active construct transfection, NF-κB and JNK reporter assays Gene Medium 10231569
2001 TLR6 functionally cooperates with TLR2 to enhance the inflammatory response to phenol-soluble modulin from Staphylococcus epidermidis; TLR1 inhibits the same TLR2-mediated response, demonstrating opposing functional interactions with TLR2. Transfection of TLR constructs into reporter cells, NF-κB activation assays, gain-of-function co-expression Journal of immunology High 11123271
2004 TLR2 and TLR6 together mediate NF-κB activation and apoptosis in response to mycoplasmal diacylated lipoproteins and MALP-2; apoptosis requires MyD88, FADD, and p38 MAPK downstream of TLR2/TLR6. Co-transfection of TLR2 and TLR6 in HEK293 cells, dominant-negative MyD88/FADD/IRAK-4 constructs, caspase-8 activation assay, p38 MAPK inhibitor Cellular microbiology High 14706104
2005 TLR6 is expressed on the surface of human monocytes, monocyte-derived immature dendritic cells, and neutrophils (but not B, T, or NK cells), where it co-localizes with TLR2 at the plasma membrane; TLR2/TLR6 signaling occurs at the cell surface without requiring endosomal maturation, and TLR6 is required for recognition of diacylated lipopeptide (MALP-2) and peptidoglycan. Function-blocking anti-TLR6 mAb generation, flow cytometry, confocal microscopy, cytokine inhibition assay, TLR2 Cys mutant analysis Journal of immunology High 15661917
2005 Mycoplasma pneumoniae F0F1-ATPase, a dipalmitoylated lipoprotein, activates NF-κB through TLR2 in cooperation with both TLR1 and TLR6; the lipid moiety (not the protein) is the active component. Dominant-negative TLR1 and TLR6 constructs in THP-1 cells, lipoprotein lipase treatment, NF-κB activation assay Journal of immunology Medium 16177110
2006 Heterodimerization of TLR2 with TLR1 or TLR6 expands the lipopeptide ligand spectrum without inducing different downstream signaling cascades; all TLR2 heterodimers use the same signaling cascade (same MAPK activation and gene expression profile). Dominant-negative signaling molecule constructs, MAPK immunoblotting, microarray gene expression analysis, multiple synthetic lipopeptide ligands Journal of leukocyte biology High 18056480
2007 Innate immune responses to endosymbiotic Wolbachia in Brugia malayi and Onchocerca volvulus filaria are dependent on TLR2-TLR6 heterodimerization and are mediated by adaptor molecules MyD88 and TIRAP/Mal, but not TLR4, TRIF, or TRAM. TLR and adaptor molecule knockout macrophages (TLR2-/-, TLR4-/-, TLR6-/-, MyD88-/-, TIRAP/Mal-/-, TRIF-/-, TRAM-/-), cytokine production assays, in vivo macrophage migration assay Journal of immunology High 17202370
2007 HIF-1α directly binds to HIF-1 binding sites in the TLR6 (and TLR2) promoter and coordinately induces TLR6 expression during hypoxia; conditional HIF-1α knockout abolishes hypoxia-induced TLR6 upregulation in vivo. Chromatin immunoprecipitation (ChIP), promoter analysis, HIF-1 loss- and gain-of-function mouse models, RT-PCR, protein expression in multiple cell lines PloS one High 18159247
2008 TLR6 blocks TLR1/TLR2-mediated apoptosis in trophoblasts exposed to peptidoglycan, redirecting the response toward NF-κB activation and IL-8/IL-6 secretion; TLR6 thus acts as a functional modulator of TLR1/TLR2 signaling in first trimester trophoblasts. In vitro human first trimester trophoblast model, antibody blocking experiments, NF-κB activation assay, cytokine ELISA Journal of immunology Medium 18424724
2008 The Chlamydia trachomatis macrophage infectivity potentiator (Mip) lipoprotein activates proinflammatory cytokines through TLR2/TLR1/TLR6 and CD14, but not TLR4; the lipid modification (not protein backbone) is required for this activity. Lipase treatment of Mip, non-lipidated C20A mutant analysis, TLR-blocking experiments, ELISA cytokine measurement Journal of immunology Medium 18178856
2009 MVA poxvirus innate immune sensing in macrophages is mediated by the TLR2-TLR6-MyD88 pathway (for IFNβ-independent chemokine production), MDA-5-IPS-1 (for IFNβ), and NALP3 inflammasome (for IL-1β processing); TLR2/TLR6/MyD88 is required for transcription of the Il1b gene. Knockout macrophages (TLR2-/-, TLR6-/-, MyD88-/-, TRIF-/-, NALP3-/-), shRNA knockdown of RLRs and inflammasome components, cytokine profiling PLoS pathogens High 19543380
2011 TLR6 signaling (but not TLR2) is specifically required for M. leprae-induced lipid droplet biogenesis in Schwann cells and for bacterial uptake; TLR6-dependent LD formation correlates with increased PGE2 and IL-10 and reduced IL-12 and NO production, promoting bacterial persistence. TLR6 knockout Schwann cells, inhibitor studies (C-75 fatty acid synthase inhibitor), cytokine ELISA, confocal microscopy of patient nerve sections Journal of immunology High 21813774
2011 TLR6 activation is required for IL-23 production and Th17 responses in dendritic cells; Tlr6-/- mice show impaired IL-23 and IL-17A levels and reduced dectin-1 expression during fungal asthma, and exogenous IL-23 rescues these defects. Tlr6-/- mouse models of Aspergillus fumigatus and house dust mite-induced asthma, in vitro DC stimulation assays, exogenous IL-23 treatment rescue experiment Journal of clinical investigation High 22005301
2012 The TLR2 R753Q polymorphism impairs agonist-induced tyrosine phosphorylation of TLR2, heterodimerization with TLR6, and recruitment of adaptor proteins MyD88 and Mal/TIRAP, resulting in deficient NF-κB activation, p38 phosphorylation, and IL-8 induction. Transfection of WT vs R753Q TLR2 in HEK293 cells, co-immunoprecipitation for TLR2/TLR6 dimerization, tyrosine phosphorylation immunoblotting, molecular modeling, NF-κB reporter assay Journal of biological chemistry High 22992740
2014 Crystal structure of the TIR domain of TLR6 at 2.2 Å resolution reveals a novel homo-dimerization interface critical for interaction with TIR-containing adaptor proteins; structural comparisons identify similarities and differences with other TLR TIR domains. X-ray crystallography at 2.2 Å resolution, structural comparison with other TIR domains Journal of molecular biology High 25088687
2015 Dengue virus NS1 protein activates TLR2 and TLR6 on PBMCs, leading to IL-6 and TNF-α production; blocking TLR2 or TLR6 reduces NS1-stimulated cytokine production. TLR6-/- mice show higher survivability upon DV or NS1 challenge compared to wild-type mice. Neutralizing antibody blocking, SEAP reporter assay, TLR6-/- mouse survival experiment, ELISA, flow cytometry PLoS pathogens Medium 26226614
2015 The diacylated lipopeptide BPPcysMPEG signals through TLR2-TLR6 heterodimer (but not TLR1-TLR2) to selectively activate p38MAPK/ATF2, increase IL-12 and iNOS expression, and confer antileishmanial protection; TLR2-TLR2 homodimerization increases while TLR2-TLR6 dimerization decreases during L. major infection. Lentivirus-expressed shRNA knockdown of TLR1, TLR2, TLR6 in BALB/c mice, co-immunoprecipitation of TLR2 dimers, p38MAPK/ATF2 activation assays, cytokine ELISA, parasite burden measurement Journal of immunology High 25194056
2017 TLR4 and TLR6 form a functional heterodimer at the plasma membrane induced by Aβ peptides; the transmembrane domains of TLR4 and TLR6 are essential for receptor dimerization and activation; inhibiting TLR4-TLR6 assembly using a TLR4-derived peptide reduces proinflammatory mediator secretion from microglia and rescues neurons from death. Transmembrane peptide interference with dimerization, co-immunoprecipitation, proinflammatory mediator assays in microglia, neuronal death rescue experiment Journal of biological chemistry Medium 28655763
2017 Dengue virus NS1 expressed in eukaryotic cells activates immune cells via TLR4 but NOT via TLR2/TLR6; the previously reported TLR2/6 activation by NS1 was attributed to misfolded/contaminated E. coli-derived recombinant NS1 preparations. TLR knockout macrophages (TLR4-/-, TLR2-/-, TLR6-/-), TLR-blocking antibodies in human PBMCs, properly folded eukaryotic NS1 vs E. coli-derived NS1 Immunology and cell biology High 28220810
2023 TLR6 is required for MyD88-dependent mitigation of hematopoietic acute radiation syndrome; the synthetic TLR2/TLR6 ligand FSL-1 promotes hematopoietic progenitor cell proliferation and red blood cell development via TLR2/TLR6-MyD88 signaling in mice and nonhuman primates. Subcutaneous FSL-1 administration in mice and nonhuman primates after radiation; MyD88-dependent mechanism established from prior work; bone marrow aspirate cytology, hematopoietic recovery assays PNAS Medium 38051771
2024 Persistent H. pylori infection reduces TLR6 sensitivity to bacterial components, inducing immune tolerance via the TLR6/JNK signaling pathway; restoration of TLR6 expression potentiates IL-1β and IL-8 production and reduces H. pylori colonization in vivo. Sustained H. pylori exposure model in GES-1 cells (1–30 generations) and Mongolian gerbils (5–90 weeks), TLR6 overexpression rescue, cytokine measurement, in vivo bacterial colonization assay Gastric cancer Medium 38310631
2015 Vibrio cholerae cytolysin (VCC) in transmembrane oligomeric form triggers proinflammatory responses in monocytes and macrophages via TLR2/TLR6-dependent signaling involving MyD88/IRAK1/TRAF6, NF-κB, and JNK; p38 MAPK was not required. TLR2/TLR6 stimulation with VCC oligomers assembled in liposome membranes, pathway inhibitor studies, NF-κB and JNK activation assays Biochemical journal Medium 25431887
2023 BacSp222 bacteriocin is a novel ligand for the TLR2/TLR6 heterodimer (but not TLR2/TLR1, TLR4, or TLR5); it activates NF-κB through TLR2/TLR6, undergoes internalization into cells, and induces MyD88/NF-κB-dependent proinflammatory signaling. HEK-Blue reporter cells overexpressing TLR2, TLR2/TLR1, TLR2/TLR6; TLR2 antagonist experiments; confocal microscopy for internalization; TNF assay in macrophage lines Inflammation research Medium 36964784

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Cutting edge: functional interactions between toll-like receptor (TLR) 2 and TLR1 or TLR6 in response to phenol-soluble modulin. Journal of immunology (Baltimore, Md. : 1950) 346 11123271
1999 TLR6: A novel member of an expanding toll-like receptor family. Gene 296 10231569
2009 Innate immune sensing of modified vaccinia virus Ankara (MVA) is mediated by TLR2-TLR6, MDA-5 and the NALP3 inflammasome. PLoS pathogens 253 19543380
2007 Heterodimerization of TLR2 with TLR1 or TLR6 expands the ligand spectrum but does not lead to differential signaling. Journal of leukocyte biology 252 18056480
2006 TLR1- and TLR6-independent recognition of bacterial lipopeptides. The Journal of biological chemistry 204 16455646
2005 TLR1 and TLR6 polymorphisms are associated with susceptibility to invasive aspergillosis after allogeneic stem cell transplantation. Annals of the New York Academy of Sciences 166 16461792
2007 Hypoxia inducible factor (HIF)-1 coordinates induction of Toll-like receptors TLR2 and TLR6 during hypoxia. PloS one 155 18159247
2005 A dipalmitoylated lipoprotein from Mycoplasma pneumoniae activates NF-kappa B through TLR1, TLR2, and TLR6. Journal of immunology (Baltimore, Md. : 1950) 142 16177110
2003 Mycobacterial infection in TLR2 and TLR6 knockout mice. Microbiology and immunology 137 12825894
2004 Stimulation of human Toll-like receptor (TLR) 2 and TLR6 with membrane lipoproteins of Mycoplasma fermentans induces apoptotic cell death after NF-kappa B activation. Cellular microbiology 126 14706104
2005 Sequence variants in Toll-like receptor gene cluster (TLR6-TLR1-TLR10) and prostate cancer risk. Journal of the National Cancer Institute 124 15812078
2014 Epithelial and stromal cells of bovine endometrium have roles in innate immunity and initiate inflammatory responses to bacterial lipopeptides in vitro via Toll-like receptors TLR2, TLR1, and TLR6. Endocrinology 116 24437488
2015 Activation of TLR2 and TLR6 by Dengue NS1 Protein and Its Implications in the Immunopathogenesis of Dengue Virus Infection. PLoS pathogens 104 26226614
2011 TLR6-driven lipid droplets in Mycobacterium leprae-infected Schwann cells: immunoinflammatory platforms associated with bacterial persistence. Journal of immunology (Baltimore, Md. : 1950) 92 21813774
2005 Surface-expressed TLR6 participates in the recognition of diacylated lipopeptide and peptidoglycan in human cells. Journal of immunology (Baltimore, Md. : 1950) 91 15661917
2017 Dengue virus NS1 protein activates immune cells via TLR4 but not TLR2 or TLR6. Immunology and cell biology 89 28220810
2007 Innate immune responses to endosymbiotic Wolbachia bacteria in Brugia malayi and Onchocerca volvulus are dependent on TLR2, TLR6, MyD88, and Mal, but not TLR4, TRIF, or TRAM. Journal of immunology (Baltimore, Md. : 1950) 88 17202370
2016 Identification of TLR2/TLR6 signalling lactic acid bacteria for supporting immune regulation. Scientific reports 85 27708357
2008 The proinflammatory cytokine response to Chlamydia trachomatis elementary bodies in human macrophages is partly mediated by a lipoprotein, the macrophage infectivity potentiator, through TLR2/TLR1/TLR6 and CD14. Journal of immunology (Baltimore, Md. : 1950) 84 18178856
2011 Association of human TLR1 and TLR6 deficiency with altered immune responses to BCG vaccination in South African infants. PLoS pathogens 81 21852947
2007 Role of TLR1 and TLR6 in the host defense against disseminated candidiasis. FEMS immunology and medical microbiology 81 18036178
2008 Genetic variation in the toll-like receptor gene cluster (TLR10-TLR1-TLR6) and prostate cancer risk. International journal of cancer 79 18752252
2004 Toll-like receptor 6 gene (TLR6): single-nucleotide polymorphism frequencies and preliminary association with the diagnosis of asthma. Genes and immunity 74 15266299
2008 TLR6 modulates first trimester trophoblast responses to peptidoglycan. Journal of immunology (Baltimore, Md. : 1950) 71 18424724
2011 The protective role of TLR6 in a mouse model of asthma is mediated by IL-23 and IL-17A. The Journal of clinical investigation 68 22005301
2012 R753Q polymorphism inhibits Toll-like receptor (TLR) 2 tyrosine phosphorylation, dimerization with TLR6, and recruitment of myeloid differentiation primary response protein 88. The Journal of biological chemistry 67 22992740
2006 Biased distribution of single nucleotide polymorphisms (SNPs) in porcine Toll-like receptor 1 (TLR1), TLR2, TLR4, TLR5, and TLR6 genes. Immunogenetics 67 16604477
2015 Association of TLR1, TLR2, TLR4, TLR6, and TIRAP polymorphisms with disease susceptibility. Immunologic research 61 25784622
2014 Crystal structure of TIR domain of TLR6 reveals novel dimeric interface of TIR-TIR interaction for toll-like receptor signaling pathway. Journal of molecular biology 57 25088687
2012 Variation in the TLR10/TLR1/TLR6 locus is the major genetic determinant of interindividual difference in TLR1/2-mediated responses. Genes and immunity 55 23151486
2012 Genetic variation in the Toll-like receptor gene cluster (TLR10-TLR1-TLR6) influences disease course in sarcoidosis. Tissue antigens 53 22150367
2003 Porcine TLR2 and TLR6: identification and their involvement in Mycoplasma hyopneumoniae infection. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 53 14585198
2017 Role of TLR1, TLR2 and TLR6 in the modulation of intestinal inflammation and Candida albicans elimination. Gut pathogens 49 28289440
2016 A new non-phagocytic TLR6 with broad recognition ligands from Pacific oyster Crassostrea gigas. Developmental and comparative immunology 49 27443817
2015 TLR9 is required for MAPK/NF-κB activation but does not cooperate with TLR2 or TLR6 to induce host resistance to Brucella abortus. Journal of leukocyte biology 49 26578650
2012 Atherosclerosis induced by endogenous and exogenous toll-like receptor (TLR)1 or TLR6 agonists. Journal of lipid research 46 22822027
2007 Gene conversion limits divergence of mammalian TLR1 and TLR6. BMC evolutionary biology 45 17727694
2014 TLR1, TLR2, and TLR6 gene polymorphisms are associated with increased susceptibility to complicated skin and skin structure infections. The Journal of infectious diseases 40 24511099
2004 Long-term control of Mycobacterium bovis BCG infection in the absence of Toll-like receptors (TLRs): investigation of TLR2-, TLR6-, or TLR2-TLR4-deficient mice. Infection and immunity 39 15557622
2014 Pegylated bisacycloxypropylcysteine, a diacylated lipopeptide ligand of TLR6, plays a host-protective role against experimental Leishmania major infection. Journal of immunology (Baltimore, Md. : 1950) 38 25194056
2017 Intramembrane attenuation of the TLR4-TLR6 dimer impairs receptor assembly and reduces microglia-mediated neurodegeneration. The Journal of biological chemistry 35 28655763
2007 Association between Toll-like receptor gene cluster (TLR6, TLR1, and TLR10) and prostate cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 35 17932345
2011 Polymorphisms in the TLR6 gene associated with the inverse association between childhood acute lymphoblastic leukemia and atopic disease. Leukemia 34 22134717
2013 The molecular basis for recognition of bacterial ligands at equine TLR2, TLR1 and TLR6. Veterinary research 33 23826682
2015 Hepatitis C Virus NS3 Mediated Microglial Inflammation via TLR2/TLR6 MyD88/NF-κB Pathway and Toll Like Receptor Ligand Treatment Furnished Immune Tolerance. PloS one 32 25965265
2010 Sequence variants in the TLR4 and TLR6-1-10 genes and prostate cancer risk. Results based on pooled analysis from three independent studies. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 29 20200442
2017 The interaction between farming/rural environment and TLR2, TLR4, TLR6 and CD14 genetic polymorphisms in relation to early- and late-onset asthma. Scientific reports 28 28262750
2009 Synergism of toll-like receptor 2 (TLR2), TLR4, and TLR6 ligation on the production of tumor necrosis factor (TNF)-alpha in a spontaneous arthritis animal model of interleukin (IL)-1 receptor antagonist-deficient mice. Immunology letters 28 19428561
2006 Genomic organization and transcript profiling of the bovine toll-like receptor gene cluster TLR6-TLR1-TLR10. Gene 28 16950576
2020 Baicalin ameliorates Mycoplasma gallisepticum-induced lung inflammation in chicken by inhibiting TLR6-mediated NF-κB signalling. British poultry science 27 33252265
2020 Polydatin attenuates Mycoplasma gallisepticum (HS strain)-induced inflammation injury via inhibiting the TLR6/ MyD88/NF-κB pathway. Microbial pathogenesis 26 33010363
2009 European wild boars and domestic pigs display different polymorphic patterns in the Toll-like receptor (TLR) 1, TLR2, and TLR6 genes. Immunogenetics 25 19953243
2005 Sublethal infection of C57BL/6 mice with Salmonella enterica Serovar Typhimurium leads to an increase in levels of Toll-like receptor 1 (TLR1), TLR2, and TLR9 mRNA as well as a decrease in levels of TLR6 mRNA in infected organs. Infection and immunity 22 15731092
2024 Sustained exposure to Helicobacter pylori induces immune tolerance by desensitizing TLR6. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 20 38310631
2021 Interaction of Ectodomain of Respiratory Syncytial Virus G Protein with TLR2/ TLR6 Heterodimer: An In vitro and In silico Approach to Decipher the Role of RSV G Protein in Pro-inflammatory Response against the Virus. Current pharmaceutical design 20 34279194
2015 Transmembrane oligomeric form of Vibrio cholerae cytolysin triggers TLR2/TLR6-dependent proinflammatory responses in monocytes and macrophages. The Biochemical journal 20 25431887
2020 MMP9, CXCR1, TLR6, and MPO participant in the progression of coronary artery disease. Journal of cellular physiology 19 32052443
2020 Puerarin inhibits Mycoplasma gallisepticum (MG-HS)-induced inflammation and apoptosis via suppressing the TLR6/MyD88/NF-κB signal pathway in chicken. International immunopharmacology 18 33182066
2019 MicroRNA-494-3p alleviates inflammatory response in sepsis by targeting TLR6. European review for medical and pharmacological sciences 18 31002148
2019 gga-miR-146c Activates TLR6/MyD88/NF-κB Pathway through Targeting MMP16 to Prevent Mycoplasma Gallisepticum (HS Strain) Infection in Chickens. Cells 18 31137698
2013 Association of a common TLR-6 polymorphism with coronary artery disease - implications for healthy ageing? Immunity & ageing : I & A 18 24498948
2023 The TLR2/TLR6 ligand FSL-1 mitigates radiation-induced hematopoietic injury in mice and nonhuman primates. Proceedings of the National Academy of Sciences of the United States of America 16 38051771
2018 Novel sequence variants in the TLR6 gene associated with advanced breast cancer risk in the Saudi Arabian population. PloS one 16 30388713
2012 Mice fed with a high fat diet show a decrease in the expression of "toll like receptor (TLR)2 and TLR6 mRNAs in adipose and hepatic tissues. Nutricion hospitalaria 16 23165562
2018 Arctigenin Induces an Activation Response in Porcine Alveolar Macrophage Through TLR6-NOX2-MAPKs Signaling Pathway. Frontiers in pharmacology 15 29867481
2017 Mushroom lectin overcomes hepatitis B virus tolerance via TLR6 signaling. Scientific reports 15 28724955
2016 Toll-like receptor-6 (TLR6) deficient mice are protected from myocardial fibrosis induced by high fructose feeding through anti-oxidant and inflammatory signaling pathway. Biochemical and biophysical research communications 15 26940740
2014 Polymorphisms in TLR1, TLR6 and TLR10 genes and the risk of Graves' disease. Autoimmunity 15 25028161
2009 Analysis of NOD1, NOD2, TLR1, TLR2, TLR4, TLR5, TLR6 and TLR9 genes in anal furunculosis of German shepherd dogs. Tissue antigens 14 19254256
2021 A 192 bp ERV fragment insertion in the first intron of porcine TLR6 may act as an enhancer associated with the increased expressions of TLR6 and TLR1. Mobile DNA 11 34407874
2017 Toll like receptors TLR1/2, TLR6 and MUC5B as binding interaction partners with cytostatic proline rich polypeptide 1 in human chondrosarcoma. International journal of oncology 10 29138803
2013 Genome-wide screening identifies Plasmodium chabaudi-induced modifications of DNA methylation status of Tlr1 and Tlr6 gene promoters in liver, but not spleen, of female C57BL/6 mice. Parasitology research 10 23949311
2023 TLR-1, TLR-2, and TLR-6 MYD88-dependent signaling pathway: A potential factor in the interaction of high-DNA fragmentation human sperm with fallopian tube epithelial cells. Clinical and experimental reproductive medicine 9 36935411
2014 Testosterone persistently dysregulates hepatic expression of Tlr6 and Tlr8 induced by Plasmodium chabaudi malaria. Parasitology research 9 25056943
2021 Synergistic effect of genetic polymorphisms in TLR6 and TLR10 genes on the risk of pulmonary tuberculosis in a Moldavian population. Innate immunity 8 34275341
2017 Association of MBL2, TLR1, TLR2 and TLR6 Polymorphisms With Production of IFN-γ and IL-12 in BCG Osteitis Survivors R1. The Pediatric infectious disease journal 8 27755461
2015 7α-Hydroxycholesterol Elicits TLR6-Mediated Expression of IL-23 in Monocytic Cells. Biomolecules & therapeutics 8 25593648
2023 BacSp222 bacteriocin as a novel ligand for TLR2/TLR6 heterodimer. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 7 36964784
2019 Development of N-Acetylated Dipalmitoyl-S-Glyceryl Cysteine Analogs as Efficient TLR2/TLR6 Agonists. Molecules (Basel, Switzerland) 7 31569697
2016 Involvement of TLR6 in the induction of COX-2, PGE2 and IL-10 in macrophages by lipids from virulent S2P and attenuated R1A Babesia bovis strains. Veterinary parasitology 7 27198789
2023 Investigating the link between miR-34a-5p and TLR6 signaling in sepsis-induced ARDS. 3 Biotech 6 37496978
2005 Involvement of TLR6/1 in rLcrV-mediated immunomodulation of murine peritoneal macrophages in vitro. Molecular immunology 6 15781113
2017 MALP-2, an agonist of TLR6, promotes the immune status without affecting the differentiation capacity of umbilical cord mesenchymal stem cells. Experimental and therapeutic medicine 5 29285089
2015 Structural characterisation of Toll-like receptor 1 (TLR1) and Toll-like receptor 6 (TLR6) in elephant and harbor seals. Veterinary immunology and immunopathology 5 26827833
2023 Increased Expression of Toll-Like Receptor (TLR) 2 and TLR6 on Peripheral Blood Monocytes by Induction of Staphylococcal Enterotoxin B During Exacerbation of Atopic Dermatitis Patients. Clinical, cosmetic and investigational dermatology 3 36748066
2023 Single Nucleotide Variants in the TLR1, TLR2 and TLR6 Genes: A Case-Control Study in a Colombian Population. Tropical medicine and infectious disease 3 37888601
2019 Lesion size is associated with genetic polymorphisms in TLR1, TLR6, and TIRAP genes in patients with major abscesses and diabetic foot infections. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 3 31786695
2013 Association of TLR6 single nucleotide polymorphisms and clinical features of ischemic stroke in Korean population. Journal of exercise rehabilitation 3 24409430
2025 The Novel Role of the Expression of Toll-like Receptors TLR-5, TLR-6, and TLR-9 and Associated Up-Regulation of Programmed Cell Death 1 Receptor (PD-1) and Its Ligand (PD-L1) in Lung Sepsis. International journal of molecular sciences 2 40076895
2025 Features of toll-like receptor genes (TLR-2, TLR-3, TLR-4 and TLR-6) polymorphism in open-angle glaucoma patients. Vavilovskii zhurnal genetiki i selektsii 2 40144379
2021 Human genetic diversity regulating the TLR10/TLR1/TLR6 locus confers increased cytokines in response to Chlamydia trachomatis. HGG advances 2 35047856
2016 TLR-6 SNP P249S is associated with healthy aging in nonsmoking Eastern European Caucasians - A cohort study. Immunity & ageing : I & A 2 26997964
2025 Lacticaseibacillus rhamnosus LGG Suppresses Osteoclastogenesis via TLR6/NF-κB Modulation and Attenuates Ovariectomy-Induced Bone Loss in Mice. Probiotics and antimicrobial proteins 1 41026405
2024 Deleterious intestinal inflammation in neonatal mice treated with TLR2/TLR6 agonists. Journal of leukocyte biology 1 38872374
2017 Mycobacterium lepraemurium uses TLR-6 and MR, but not lipid rafts or DC-sign, to gain access into mouse macrophages. International journal of mycobacteriology 1 28317806
2026 A Genetic Variant of TLR6 Predicts HBsAg Decline After Pegylated Interferon-Alpha Treatment in HBeAg-Positive Chronic Hepatitis B. Journal of medical virology 0 41823038
2025 Innate Immunity Toll-Like Triad TLR6-1-10 and Its Diversity in Distinct Horse Breeds. Veterinary medicine and science 0 39918481
2025 Inhibitory Effect of a Novel Non-Steroidal AMPamide on Inflammation and Sebogenesis by Suppressing TLR4 and TLR6-Mediated Signaling Pathway. Biomolecules & therapeutics 0 40765207
2025 The effect of combination therapy on Bevacizumab, Carmustine, and Metformin chemotherapy drugs on the fluctuating performance expression of TLR2, TLR6, and IL-6 genes in the cell line of brain glioblastoma. Cancer cell international 0 41225557
2010 Single nucleotide polymorphisms and haplotypes of TLR6 gene in Chinese Cantonese population. International journal of immunogenetics 0 20402822

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