ArticlePLoS pathogens2010
Pathogen specific, IRF3-dependent signaling and innate resistance to human kidney infection.
Article in PLoS pathogens, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- A Systematic Review of the (Un)known Host Immune Response Biomarkers for Predicting Recurrence of Urinary Tract Infection.Frontiers in medicine · 2022Pooled it
- Targeting the Disease Response With NlpD and LytM for Effective Nonantibiotic Treatment of Urinary Tract Infections.The Journal of infectious diseases · 2026Article
- Urinary tract infections in children.Nature reviews. Urology · 2026Review
- How Does Biological Sex Impact Mucosal Bacterial Infection? Mucosal Defenses and Bacterial Detection.Immunological reviews · 2026Review
- More than an infection: the ecological puzzle of recurrent urinary tract infections.Frontiers in cellular and infection microbiology · 2026Review
- Molecular analysis of acute pyelonephritis-excessive innate and attenuated adaptive immunity.Life science alliance · 2025Article
- Multitarget mechanism of MYC inhibition by the bacterial lon protease in disease.Scientific reports · 2025Article
- Therapeutic Effects of IL-1RA against Acute Bacterial Infections, including Antibiotic-Resistant Strains.Pathogens (Basel, Switzerland) · 2023Article
- Uropathogen and host responses in pyelonephritis.Nature reviews. Nephrology · 2023Review
- Immunomodulation therapy offers new molecular strategies to treat UTI.Nature reviews. Urology · 2022Review
- Molecular determinants of disease severity in urinary tract infection.Nature reviews. Urology · 2021Review
- Active bacterial modification of the host environment through RNA polymerase II inhibition.The Journal of clinical investigation · 2021Article
- A host receptor enables type 1 pilus-mediated pathogenesis of Escherichia coli pyelonephritis.PLoS pathogens · 2021Article
- Innate immunity and urinary tract infection.Pediatric nephrology (Berlin, Germany) · 2020Review
- Hepatitis E Virus ORF2 Inhibits RIG-I Mediated Interferon Response.Frontiers in microbiology · 2020Article
- Mitochondrial Damage and Activation of the STING Pathway Lead to Renal Inflammation and Fibrosis.Cell metabolism · 2019Article
- Fimbriae reprogram host gene expression - Divergent effects of P and type 1 fimbriae.PLoS pathogens · 2019Article
- Whole Transcriptome Analysis of Renal Intercalated Cells Predicts Lipopolysaccharide Mediated Inhibition of Retinoid X Receptor alpha Function.Scientific reports · 2019Article
- Identification and characterization of the myeloid differentiation factor 88 gene in yellow catfish.3 Biotech · 2018Article
- A Putative Role of Apolipoprotein L1 Polymorphism in Renal Parenchymal Scarring Following Febrile Urinary Tract Infection in Nigerian Under-Five Children: Proposal for a Case-Control Association Study.JMIR research protocols · 2018Article
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mucosal immune system identifies and fights invading pathogens, while allowing non-pathogenic organisms to persist. Mechanisms of pathogen/non-pathogen discrimination are poorly understood, as is the contribution of human genetic variation in disease susceptibility. We describe here a new, IRF3-dependent signaling pathway that is critical for distinguishing pathogens from normal flora at the mucosal barrier. Following uropathogenic E. coli infection, Irf3(-/-) mice showed a pathogen-specific increase in acute mortality, bacterial burden, abscess formation and renal damage compared to wild type mice. TLR4 signaling was initiated after ceramide release from glycosphingolipid receptors, through TRAM, CREB, Fos and Jun phosphorylation and p38 MAPK-dependent mechanisms, resulting in nuclear translocation of IRF3 and activation of IRF3/IFNβ-dependent antibacterial effector mechanisms. This TLR4/IRF3 pathway of pathogen discrimination was activated by ceramide and by P-fimbriated E. coli, which use ceramide-anchored glycosphingolipid receptors. Relevance of this pathway for human disease was supported by polymorphic IRF3 promoter sequences, differing between children with severe, symptomatic kidney infection and children who were asymptomatic bacterial carriers. IRF3 promoter activity was reduced by the disease-associated genotype, consistent with the pathology in Irf3(-/-) mice. Host susceptibility to common infections like UTI may thus be strongly influenced by single gene modifications affecting the innate immune response.
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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.