Toll-like receptor (TLR2, TLR4) polymorphisms and their influence on the incidence of urinary tract infections in children with and without urinary tract malformation

Anna Krakowska; Maciej Cedzyński; Agnieszka Wosiak; Rafal Swiechowski; Adrian Krygier; Marcin Tkaczyk; Krzysztof Zeman

doi:10.5114/ceji.2022.119625

Toll-like receptor (TLR2, TLR4) polymorphisms and their influence on the incidence of urinary tract infections in children with and without urinary tract malformation

Cent Eur J Immunol. 2022;47(3):260-266. doi: 10.5114/ceji.2022.119625. Epub 2022 Sep 21.

Authors

Anna Krakowska¹, Maciej Cedzyński², Agnieszka Wosiak³, Rafal Swiechowski⁴, Adrian Krygier⁴, Marcin Tkaczyk¹, Krzysztof Zeman¹

Affiliations

¹ Department of Paediatrics, Immunology and Nephrology, Polish Mother's Memorial Hospital Research Institute, Lodz, Poland.
² Institute of Medical Biology, Polish Academy of Sciences, Lodz, Poland.
³ Institute of Information Technology, Lodz University of Technology, Lodz, Poland.
⁴ Laboratory Diagnostics Center, Polish Mother's Memorial Hospital Research Institute, Lodz, Poland.

Abstract

Introduction: Toll-like receptors (TLRs) contribute to the innate immune system. They are an element of non-specific immunity, which enables organisms to react quickly to foreign antigens, without being previously exposed to them. TLRs are pattern recognition receptors. TLR gene polymorphisms are widely investigated in connection with various infections. The aims of the study were: to investigate the role of TLR2 and TLR4 polymorphisms in the course of urinary tract infections (UTIs); to test for differences in distribution of these polymorphisms between children with urinary tract malformations suffering from recurrent UTI (rUTI), children with malformations but without rUTI and healthy controls; to determine whether these polymorphisms predispose to rUTI; and to analyse how polymorphisms and urine neutrophil gelatinase-associated lipocalin (NGAL) and interleukin 8 (IL-8) concentrations affect one another.

Material and methods: The group consisted of 133 children (1-18 years old), 68 female and 65 male. The group was divided into 4 subgroups: A (rUTI with urinary tract malformations), B (urinary tract malformations without rUTI), C (rUTI) and D (healthy controls). Polymorphisms were analysed using PCR-RFLP. IL-8 and NGAL urine concentrations were established using immunoenzymatic methods.

Results: TLR2 Arg753Gln and TLR4 Arg299Gly appeared significantly more often among children with rUTI. No correlation between urine IL-8 and urine NGAL and polymorphisms was found. Urine NGAL concentration was significantly higher among children with urinary tract malformations.

Conclusions: TLR2 Arg753Gln and TLR4 Asp299Gly may predispose to rUTI. Urine NGAL concentration suggests the presence of kidney tissue injury, of varying degrees, among children with urinary tract malformations.

Keywords: TLR2; TLR4; children; polymorphism; urinary tract infections.