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| Status |
Public on Jul 21, 2019 |
| Title |
Host susceptibility to recurrent cystitis is shaped by bladder TNF-alpha signaling dynamics |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Urinary tract infections (UTI) are common and recurrent. Both host genetics and UTI history impact susceptibility to recurrent UTI (rUTI) in women and in animal models. To identify shared patterns of host response that correlate with susceptibility, we investigated bladder inflammatory and transcriptional kinetics in acute and rUTI models. We found that TNFɑ signaling kinetics differed with mouse strain and infection history. Mice resistant to severe UTI/rUTI displayed a robust TNFɑ-dependent inflammation during the first 6 hours of acute cystitis, which waned by 24 hours; mice that are susceptible varied in their early responses but were prone to severe inflammation at 24 hours post-infection. Depletion of TNFɑ in an rUTI model revealed that early TNFɑ signaling promoted colonization resistance via exfoliation of infected bladder cells, but prolonged TNFɑ signaling exacerbated inflammation, thereby worsening infection. Host genetics and disease history impacts susceptibility by regulating the kinetics of a common TNFɑ pathway.
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| Overall design |
Whole bladder transcritpomes of mice from different genetic background or of different UTI histories were compared upon UPEC infection for different period of time with PBS mock infected counterparts.
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| Contributor(s) |
Yu L, O'Brien V, Dorsey D, Livny J, Roberson E, Colonna M, Caparon M, Hultgren SJ, Hannan T |
| Citation(s) |
31429405 |
| |
| Submission date |
Jul 23, 2018 |
| Last update date |
Aug 26, 2019 |
| Contact name |
Lu Yu |
| E-mail(s) |
soslucysos@gmail.com
|
| Organization name |
Washington University in St Louis
|
| Department |
Molecular Microbiology
|
| Lab |
Scott Hultgren
|
| Street address |
4905 Children’s Place/305 N. Euclid, 10260 McDonnell Pediatric Research Building
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| City |
St. Louis |
| State/province |
Missouri |
| ZIP/Postal code |
63110 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (146)
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| Relations |
| BioProject |
PRJNA482406 |
| SRA |
SRP154905 |
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