ArticleImmunology and cell biology2017
Tamm-Horsfall glycoprotein engages human Siglec-9 to modulate neutrophil activation in the urinary tract.
Article in Immunology and cell biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 33 citations in OpenAlex.
- Urinary tract infections in children.Nature reviews. Urology · 2026Review
- Recent advances in the clinical significance and physiological functions of uromodulin: a narrative review.BMC nephrology · 2026Review
- Decoding epithelial-immune cell crosstalk in uropathogenicFrontiers in microbiology · 2026Review
- Endocrine regulation of uromodulin in aging.Frontiers in endocrinology · 2026Review
- The natural immune molecules urinary Tamm-Horsfall protein and pentraxin 3 as predictors for recurrent urinary tract infection severity: a single-center self-control study.Renal failure · 2025Article
- Article
- Advances in uromodulin biology and potential clinical applications.Nature reviews. Nephrology · 2024Review
- Sialic acid in the regulation of blood cell production, differentiation and turnover.Immunology · 2024Review
- Supplementing Glucose Intake Reverses the Inflammation Induced by a High-Fat Diet by Increasing the Expression of Siglec-E Ligands on Erythrocytes.Inflammation · 2024Article
- The role of uromodulin in cardiovascular disease: a review.Frontiers in cardiovascular medicine · 2024Review
- The kidney protects against sepsis by producing systemic uromodulin.American journal of physiology. Renal physiology · 2022Article
- Ablation of Siglec-E augments brain inflammation and ischemic injury.Journal of neuroinflammation · 2022Article
- Genome-wide studies reveal factors associated with circulating uromodulin and its relationships to complex diseases.JCI insight · 2022Article
- The immune responses to differentFrontiers in immunology · 2022Review
- The glycobiology of uropathogenic E. coli infection: the sweet and bitter role of sugars in urinary tract immunity.Immunology · 2021Review
- Vaginal sialoglycan foraging by Gardnerella vaginalis: mucus barriers as a meal for unwelcome guests?Glycobiology · 2021Review
- Serum uromodulin is inversely associated with biomarkers of subclinical inflammation in the population-based KORA F4 study.Clinical kidney journal · 2021Article
- Novel Models ofMicroorganisms · 2021Article
- Glycoproteomic Analysis of Human Urinary Exosomes.Analytical chemistry · 2020Article
- Host Cathelicidin Exacerbates Group BmSphere · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Urinary tract infections are a major problem in human medicine for which better understanding of native immune defenses may reveal new pathways for therapeutic intervention. Tamm-Horsfall glycoprotein (THP), the most abundant urinary protein, interacts with bacteria including uropathogenic Escherichia coli (UPEC) as well host immune cells. In addition to its well-studied functions to antagonize bacterial colonization, we hypothesize that THP serves a critical host defense function through innate immune modulation. Using isolated human neutrophils, we found that THP binds neutrophils and that this interaction reduces reactive oxygen species generation, chemotaxis and killing of UPEC. We discovered that THP engages the inhibitory neutrophil receptor sialic acid-binding Ig-like lectin-9 (Siglec-9), and mouse functional ortholog Siglec-E, in a manner dependent on sialic acid on its N-glycan moieties. THP-null mice have significantly more neutrophils present in the urine compared with wild-type mice, both with and without the presence of inflammatory stimuli. These data support THP as an important negative regulator of neutrophil activation in the urinary tract, with dual functions to counteract bacterial colonization and suppress excessive inflammation within the urinary tract.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.