2026-10-13T03:01:30Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34074464 2026-10-05T17:59:57Z category_8 category_12 category_13 category_14 category_21 category_24 category_46 category_734 category_61 category_64 category_132 portal_5 item_type_3 month_year_10_2026

<p>Oligonucleotides used in this study.</p> Christopher C. Wells (22629956) Jeffrey S. Bourgeois (3129021) Morgan A. Williams (22629944) Klemen Strle (5819417) Linden T. Hu (13989808) Tanja Petnicki-Ocwieja (241386) Microbiology Cell Biology Genetics Molecular Biology Biotechnology Evolutionary Biology Immunology Biological Sciences not elsewhere classified Developmental Biology Cancer Infectious Diseases xlink "> toll refractory lyme arthritis nf -&# 954 like receptor 2 ikb &# 945 findings provide insight enables transient expression cd14 +&# 8201 ancestral allele signaled ancestral allele localizes tlr2 +&# 8201 restricts tlr1 intracellularly 1 complexes localize b activation compared ancestral allele tlr1 localization retained intracellularly b activation transmembrane domain specific signaling serine adjacent rs5743618 ), plasma membrane localization provides intracellular tlr2 increased risk functional contributions completely defined cell surface although tlr2 allelic variants <div><p>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.</p></div> 2026-10-05T17:59:46Z Dataset Dataset 10.1371/journal.pone.0358252.t001 https://figshare.com/articles/dataset/_p_Oligonucleotides_used_in_this_study_p_/34074464 CC BY 4.0