{
  "abstract": "Toll-like receptor 2/1 (TLR2/1) heterodimers detect triacylated lipoproteins. Although TLR2/1 complexes localize to both the plasma membrane and endosome, the functional contributions of compartment-specific signaling are not completely defined. A common human TLR1 polymorphism (rs5743618), at which one allele substitutes isoleucine for serine adjacent to the transmembrane domain, restricts TLR1 intracellularly and is associated with an increased risk of antibiotic-refractory Lyme arthritis. This mis-localization provides a model to examine how receptor positioning influences downstream signaling. Here, we investigated the rs5743618 polymorphism’s effects on TLR1 localization and compartment-specific NF-κB activation. Using a CD14+ TLR2+ HEK cell reporter system that enables transient expression of both allelic variants, we confirmed that the polymorphism is excluded from the cell surface and retained intracellularly, whereas the ancestral allele localizes to both compartments. Functionally, the ancestral allele signaled from both compartments, while the derived allele signaled exclusively from endosomes. Spatially restricted signaling exhibited influence on IkBα degradation and NF-κB activation compared with the ancestral allele. This activation was dependent on MyD88 localized at ligand-containing endosomes, establishing a role for this adapter in intracellular TLR2/1 signaling. These findings provide insight into how this common polymorphism impacts inflammatory outcomes.",
  "abstract_shown": true,
  "affiliations": [
    "Graduate Program in Immunology, Tufts Graduate School of Biomedical Sciences, Boston, Massachusetts, United States of America",
    "Tufts Lyme Disease Initiative, Tufts University School of Medicine, Boston, Massachusetts, United States of America",
    "Department of Biology and Biotechnology, Worcester Polytechnic Institute, Worcester, Massachusetts, United States of America",
    "Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, United States of America"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Christopher C. Wells"
    },
    {
      "affs": [
        1
      ],
      "name": "Jeffrey S. Bourgeois"
    },
    {
      "affs": [
        2
      ],
      "name": "Morgan A. Williams"
    },
    {
      "affs": [
        3
      ],
      "name": "Klemen Strle"
    },
    {
      "name": "Linden T. Hu"
    },
    {
      "name": "Tanja Petnicki-Ocwieja"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6q8wd36rqchkn.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0358252",
  "fulltext_url": null,
  "id": "6q8wd36rqchkn",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0358252",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2403|Immune Response and Inflammation"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Nucleic acids/RNA/Non-coding RNA/Small interfering RNA"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/DNA-binding proteins/Transcription factors"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Immune system proteins/Immune receptors/Toll-like receptors"
    ],
    [
      "plos",
      "/Biology and life sciences/Biochemistry/Proteins/Regulatory proteins/Transcription factors"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular structures and organelles/Cell membranes"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Cellular structures and organelles/Vesicles/Endosomes"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Signal transduction/Cell signaling/Membrane receptor signaling/Immune receptor signaling"
    ],
    [
      "plos",
      "/Biology and life sciences/Cell biology/Signal transduction/Immune receptors/Toll-like receptors"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Gene expression/Gene regulation/Small interfering RNA"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Gene expression/Gene regulation/Transcription factors"
    ],
    [
      "plos",
      "/Biology and life sciences/Immunology/Immune system proteins/Immune receptors/Toll-like receptors"
    ],
    [
      "plos",
      "/Biology and life sciences/Molecular biology/Molecular biology techniques/Transfection"
    ],
    [
      "plos",
      "/Medicine and health sciences/Immunology/Immune system proteins/Immune receptors/Toll-like receptors"
    ],
    [
      "plos",
      "/Research and analysis methods/Molecular biology techniques/Transfection"
    ],
    [
      "plos",
      "/Research and analysis methods/Specimen preparation and treatment/Staining/Cell staining"
    ]
  ],
  "openalex": "W7220401051",
  "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0358252&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-05",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/6q8wd36rqchkn.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:37Z",
      "native_id": "10.1371/journal.pone.0358252",
      "source": "plos",
      "url": "https://doi.org/10.1371/journal.pone.0358252"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "plos:gene expression",
      "subfield": "molecular-biology"
    },
    {
      "field": "biology",
      "origin": "plos:cell biology",
      "subfield": "cell-biology"
    },
    {
      "field": "biology",
      "origin": "plos:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Endosome restricted human TLR1 polymorphism highlights a role for MyD88 in Pam₃CSK₄ detection",
  "title_text": "Endosome restricted human TLR1 polymorphism highlights a role for MyD88 in Pam₃CSK₄ detection",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:37Z",
  "url": "https://research.draconitic.com/paper/6q8wd36rqchkn",
  "venue": "PLOS One",
  "versions": []
}