ArticleKidney international2018
Interleukin-6/Stat3 signaling has an essential role in the host antimicrobial response to urinary tract infection.
Article in Kidney international, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 2 of them syntheses that pooled it.
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Who cites it
47 citing papers in PubMed, 2 syntheses or guidelines pooled it, 73 citations in OpenAlex.
- Invasive mould disease in fatal COVID-19: a systematic review of autopsies.The Lancet. Microbe · 2021Pooled it
- Risk of Reactivation of Hepatitis B Virus (HBV) and Tuberculosis (TB) and Complications of Hepatitis C Virus (HCV) Following Tocilizumab Therapy: A Systematic Review to Inform Risk Assessment in the COVID-19 Era.Frontiers in medicine · 2021Pooled it
- Essential role for the urothelial plaque in Gram-negative urinary tract infections.Scientific reports · 2026Article
- Traditional plant urologicals curb early uropathogenic E. coli infection and strengthen host innate defense.Applied microbiology and biotechnology · 2026Article
- Decoding epithelial-immune cell crosstalk in uropathogenicFrontiers in microbiology · 2026Review
- Interleukin-6 Limits Host Susceptibility to Urinary Tract Infection by Promoting Urothelial Expulsion of Intracellular Bacteria.Journal of innate immunity · 2026Article
- CAUTIon - not all UTIs are the same.Nature reviews. Urology · 2025Review
- PTEN modulates urinary tract infection susceptibility and shapes urothelial antibacterial defenses.Life science alliance · 2025Article
- Article
- Human bladder organoids model urinary tract infection and bacteriophage therapy.bioRxiv : the preprint server for biology · 2025Article
- MyD88-mediated signaling in intestinal fibroblasts regulates macrophage antimicrobial defense and prevents dysbiosis in the gut.Cell reports · 2025Article
- Urinary Tract Infections Detection with Molecular Biomarkers.Biomolecules · 2024Review
- A Dynamic Interplay of Innate Immune Responses During Urinary Tract Infection.Immune network · 2024Review
- Gallic Acid Alleviates Injury of Intestine Induced by Escherichia Coli: Protective Role of Metalloproteinase and Antioxidants on Small Intestine In-vivo.Galen medical journal · 2024Article
- The urothelial gene regulatory network: understanding biology to improve bladder cancer management.Oncogene · 2024Review
- UropathogenicFrontiers in cellular and infection microbiology · 2024Article
- Unveiling Potential Biomarkers for Urinary Tract Infection: An Integrated Bioinformatics Approach.Advanced biomedical research · 2024Article
- Murine Ribonuclease 6 Limits Bacterial Dissemination during Experimental Urinary Tract Infection.Journal of innate immunity · 2024Article
- The Potential Role of Persister Cells in Urinary Tract Infections.Current urology reports · 2023Review
- Immune defenses in the urinary tract.Trends in immunology · 2023Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The signaling networks regulating antimicrobial activity during urinary tract infection (UTI) are incompletely understood. Interleukin-6 (IL-6) levels increase with UTI severity, but the specific contributions of IL-6 to host immunity against bacterial uropathogens are unknown. To clarify this we tested whether IL-6 activates the Stat3 transcription factor, to drive a program of antimicrobial peptide gene expression in infected urothelium during UTI. Transurethral inoculation of uropathogenic Escherichia coli led to IL-6 secretion, urothelial Stat3 phosphorylation, and activation of antimicrobial peptide transcription, in a Toll-like receptor 4-dependent manner in a murine model of cystitis. Recombinant IL-6 elicited Stat3 phosphorylation in primary urothelial cells in vitro, and systemic IL-6 administration promoted urothelial Stat3 phosphorylation and antimicrobial peptide expression in vivo. IL-6 deficiency led to decreased urothelial Stat3 phosphorylation and antimicrobial peptide mRNA expression following UTI, a finding mirrored by conditional Stat3 deletion. Deficiency in IL-6 or Stat3 was associated with increased formation of intracellular bacterial communities, and exogenous IL-6 reversed this phenotype in IL-6 knockout mice. Moreover, chronic IL-6 depletion led to increased renal bacterial burden and severe pyelonephritis in C3H/HeOuJ mice. Thus, IL-6/Stat3 signaling drives a transcriptional program of antimicrobial gene expression in infected urothelium, with key roles in limiting epithelial invasion and ascending infection.
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