Association of Toll-Like Receptor 4 Gene Polymorphism and Expression with Urinary Tract Infection Types in Adults

Abstract

BackgroundInnate immunity of which Toll-like receptor (TLR) 4 and CXCR1 are key elements plays a central role in the development of urinary tract infection (UTI). Although the relation between the genetics of TLR4 and CXCR1 and UTI is investigated partly, the polymorphisms and expression of TLR4 and CXCR1 in different types of UTI in adults are not extremely clear.Methodology/Principal FindingsThis study investigates the presence of TLR4 A (896) G and CXCR1 G (2608) C polymorphisms in 129 UTI patients using RFLP-PCR. Gene and allelic prevalence were compared with 248 healthy controls. Flow cytometry was used to detect TLR4 and CXCR1 expression in the monocytes of UTI patients and healthy controls. TLR4 (896) AG genotype and TLR4 (896) G allele had higher prevalence in UTI (especially in acute cystitis and urethritis) patients, whereas CXCR1 (2608) GC genotype and CXCR1 (2608) C allele had lower prevalence in UTI patients than controls. TLR4 expression was significantly lower in chronic UTI patients than in acute pyelonephritis or healthy controls. CXCR1 expression was similar in both controls and patients. TLR4 expression in chronic UTI patients after astragalus treatment was higher than pre-treatment.ConclusionsThe results indicate the relationship between the carrier status of TLR4 (896) G alleles and the development of UTI, especially acute cystitis and urethritis, in adults. TLR4 expression levels are correlated with chronic UTI.

Genetic Polymorphisms in Toll-Like Receptors among Pediatric Patients with Renal Parenchymal Infections of Different Clinical Severities

“…Previous studies have shown that single nucleotide polymorphisms (SNPs) in the TLR-2 and TLR-4 genes can affect host susceptibility to UTIs [7], [11], [13], [16]–[19]. In contrast, we did not observe this association for TLR-4 in APN and ALN [12].…”

“…Among these genes are those encoding Toll-like receptors (TLRs), which recognize pathogen-associated molecular patterns (PAMPs), and those encoding chemokines and chemokine receptors, which facilitate the migration of neutrophils to the infected urinary tract. Single gene defects or variations in these genes could confer differences in susceptibility to urinary pathogen invasion [7]–[9], [11]–[13].…”

Urinary Tract Infections and the Mucosal Immune System

“…Reduced CXCR1 or CXCR2 expression was observed in patients with onset of APN before the age of 15 years and in premenopausal women with recurrent UTI. Artifoni et al found a difference in CXCL8 SNPs between patients with dimercaptosuccinic acid scan-confirmed APN but Yin and colleagues found no difference in CXCR1 expression levels but decreased TLR4 expression in patients with history of recurrent UTIs (aged 19-80 years) compared with controls (Yin et al, 2010).…”

“…Chemokine receptor type 1 and related genes have also been examined in other UTI-prone patients (Artifoni et al, 2007;Smithson et al, 2005;Yin et al, 2010;Hawn et al, 2009). Reduced CXCR1 or CXCR2 expression was observed in patients with onset of APN before the age of 15 years and in premenopausal women with recurrent UTI.…”

Nefronia en pediatría: dentro del espectro de las infecciones urinarias. Serie clínica y revisión de la literatura

“…Defectos de un único gen o variaciones en estos genes podrían conferir diferencias en la susceptibilidad a la invasión de patógenos urinarios. En los últimos años se han publicado múltiples estudios enfocados a profundizar en esta compleja interacción hospedero-patógeno 16,17 . En relación al perfil clínico, a mayor edad aumenta significativamente el riesgo de desarrollar una lesión focal.…”