Academic Journal
Toll-like receptor 4 promoter polymorphisms: common TLR4 variants may protect against severe urinary tract infection.
| العنوان: | Toll-like receptor 4 promoter polymorphisms: common TLR4 variants may protect against severe urinary tract infection. |
|---|---|
| المؤلفون: | Bryndís Ragnarsdóttir, Klas Jönsson, Alexander Urbano, Jenny Grönberg-Hernandez, Nataliya Lutay, Martti Tammi, Mattias Gustafsson, Ann-Charlotte Lundstedt, Irene Leijonhufvud, Diana Karpman, Björn Wullt, Lennart Truedsson, Ulf Jodal, Björn Andersson, Catharina Svanborg |
| المصدر: | PLoS ONE, Vol 5, Iss 5, p e10734 (2010) |
| بيانات النشر: | Public Library of Science (PLoS), 2010. |
| سنة النشر: | 2010 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | BackgroundPolymorphisms affecting Toll-like receptor (TLR) structure appear to be rare, as would be expected due to their essential coordinator role in innate immunity. Here, we assess variation in TLR4 expression, rather than structure, as a mechanism to diversify innate immune responses.Methodology/principal findingsWe sequenced the TLR4 promoter (4,3 kb) in Swedish blood donors. Since TLR4 plays a vital role in susceptibility to urinary tract infection (UTI), promoter sequences were obtained from children with mild or severe disease. We performed a case-control study of pediatric patients with asymptomatic bacteriuria (ABU) or those prone to recurrent acute pyelonephritis (APN). Promoter activity of the single SNPs or multiple allelic changes corresponding to the genotype patterns (GPs) was tested. We then conducted a replication study in an independent cohort of adult patients with a history of childhood APN. Last, in vivo effects of the different GPs were examined after therapeutic intravesical inoculation of 19 patients with Escherichia coli 83972. We identified in total eight TLR4 promoter sequence variants in the Swedish control population, forming 19 haplotypes and 29 genotype patterns, some with effects on promoter activity. Compared to symptomatic patients and healthy controls, ABU patients had fewer genotype patterns, and their promoter sequence variants reduced TLR4 expression in response to infection. The ABU associated GPs also reduced innate immune responses in patients who were subjected to therapeutic urinary E. coli tract inoculation.ConclusionsThe results suggest that genetic variation in the TLR4 promoter may be an essential, largely overlooked mechanism to influence TLR4 expression and UTI susceptibility. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1932-6203 |
| Relation: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20505764/?tool=EBI; https://doaj.org/toc/1932-6203 |
| DOI: | 10.1371/journal.pone.0010734 |
| URL الوصول: | https://doaj.org/article/588838fafd4343628d0638680e63bd0e |
| رقم الانضمام: | edsdoj.588838fafd4343628d0638680e63bd0e |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 19326203 |
|---|---|
| DOI: | 10.1371/journal.pone.0010734 |