Dual ligand/receptor interactions activate urothelial defenses against uropathogenic E. coli
Why is this work in the frame?
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
No Canadian affiliation. An affiliation-only frame — the usual design — would never have seen this work. It is one of the works that make the case for inverting the frame.
The three-model screen
all 1,000 screened works →All three models called this out of scope.
Molecular immunology of urothelial defense against uropathogenic E. coli.
This is a biomedical study of urothelial defenses against infection.
Host–pathogen immunology study of urothelial defenses against UPEC.
Abstract
During urinary tract infection (UTI), the second most common bacterial infection, dynamic interactions take place between uropathogenic E. coli (UPEC) and host urothelial cells. While significant strides have been made in the identification of the virulence factors of UPEC, our understanding of how the urothelial cells mobilize innate defenses against the invading UPEC remains rudimentary. Here we show that mouse urothelium responds to the adhesion of type 1-fimbriated UPEC by rapidly activating the canonical NF-κB selectively in terminally differentiated, superficial (umbrella) cells. This activation depends on a dual ligand/receptor system, one between FimH adhesin and uroplakin Ia and another between lipopolysaccharide and Toll-like receptor 4. When activated, all the nuclei (up to 11) of a multinucleated umbrella cell are affected, leading to significant amplification of proinflammatory signals. Intermediate and basal cells of the urothelium undergo NF-κB activation only if the umbrella cells are detached or if the UPEC persistently express type 1-fimbriae. Inhibition of NF-κB prevents the urothelium from clearing the intracellular bacterial communities, leading to prolonged bladder colonization by UPEC. Based on these data, we propose a model of dual ligand/receptor system in innate urothelial defenses against UPEC.
Stored with the screening record, where it is evidence for the labels above.
The record
- Venue
- Scientific Reports
- Topic
- Urinary Tract Infections Management
- Field
- Medicine
- Canadian institutions
- —
- Funders
- National Institute of Diabetes and Digestive and Kidney DiseasesNational Institute of Allergy and Infectious DiseasesYork UniversityBiomedical Laboratory Research and Development, VA Office of Research and DevelopmentSchool of Medicine, New York UniversityNational Institutes of HealthOffice of Research and DevelopmentU.S. Department of Veterans Affairs
- Keywords
- ReceptorLigand (biochemistry)Cancer researchCell biologyChemistryComputational biologyBiologyGenetics
- Has abstract in OpenAlex
- yes