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Neutrophil extracellular traps in urinary tract infection

BACKGROUND: Urinary tract infections (UTI) are common types of bacterial infection in children. UTI treatment is aimed to prevent complications including hypertension, proteinuria, and progression to chronic kidney disease. Activated neutrophils release chromatin-based structures associated with ant...

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Autores principales: Krivošíková, Katarína, Šupčíková, Nadja, Gaál Kovalčíková, Alexandra, Janko, Jakub, Pastorek, Michal, Celec, Peter, Podracká, Ľudmila, Tóthová, Ľubomíra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10067609/
https://www.ncbi.nlm.nih.gov/pubmed/37020646
http://dx.doi.org/10.3389/fped.2023.1154139
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author Krivošíková, Katarína
Šupčíková, Nadja
Gaál Kovalčíková, Alexandra
Janko, Jakub
Pastorek, Michal
Celec, Peter
Podracká, Ľudmila
Tóthová, Ľubomíra
author_facet Krivošíková, Katarína
Šupčíková, Nadja
Gaál Kovalčíková, Alexandra
Janko, Jakub
Pastorek, Michal
Celec, Peter
Podracká, Ľudmila
Tóthová, Ľubomíra
author_sort Krivošíková, Katarína
collection PubMed
description BACKGROUND: Urinary tract infections (UTI) are common types of bacterial infection in children. UTI treatment is aimed to prevent complications including hypertension, proteinuria, and progression to chronic kidney disease. Activated neutrophils release chromatin-based structures associated with antimicrobial proteins called neutrophil extracellular traps (NETs). We aimed to describe the role of NET-associated markers in children with UTI as well as the role of NETs formation in a mouse model of UTI. MATERIALS AND METHODS: Markers of NETs including extracellular DNA (ecDNA), myeloperoxidase (MPO) and cathelicidin were analyzed in children with febrile UTI caused by E. coli (n = 98, aged 0.3–1.3 years) and in healthy controls (n = 50, 0.5–5.2 years). Moreover, an acute experimental model of UTI was performed on PAD4 knock-out mice with diminished NETs formation (n = 18), and on wild-type mice (n = 15). RESULTS: Children with UTI had significantly higher urinary NETs markers including total ecDNA, nuclear DNA and mitochondrial DNA, altogether with MPO and cathelicidin. The concentrations of MPO and cathelicidin positively correlated with ecDNA (r = 0.53, p ≤ 0.001; r = 0.56, p ≤ 0.001, respectively) and the number of leukocytes in the urine (r = 0.29, p ≤ 0.05; r = 0.27, p ≤ 0.05, respectively). Moreover, urinary MPO was positively associated with cathelicidin (r = 0.61, p ≤ 0.001). In the experimental model, bacterial load in the bladder (20-fold) and kidneys (300-fold) was significantly higher in PAD4 knock-out mice than in wild-type mice. CONCLUSION: Higher urinary NETs makers—ecDNA, MPO and cathelicidin and their correlation with leukocyturia in children with UTI confirmed our hypothesis about the association between NETs and UTI in children. Higher bacterial load in mice with diminished NETs formation suggests that NETs are not only a simple consequence of UTI, but might play a direct role in the prevention of pyelonephritis and other UTI complications.
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spelling pubmed-100676092023-04-04 Neutrophil extracellular traps in urinary tract infection Krivošíková, Katarína Šupčíková, Nadja Gaál Kovalčíková, Alexandra Janko, Jakub Pastorek, Michal Celec, Peter Podracká, Ľudmila Tóthová, Ľubomíra Front Pediatr Pediatrics BACKGROUND: Urinary tract infections (UTI) are common types of bacterial infection in children. UTI treatment is aimed to prevent complications including hypertension, proteinuria, and progression to chronic kidney disease. Activated neutrophils release chromatin-based structures associated with antimicrobial proteins called neutrophil extracellular traps (NETs). We aimed to describe the role of NET-associated markers in children with UTI as well as the role of NETs formation in a mouse model of UTI. MATERIALS AND METHODS: Markers of NETs including extracellular DNA (ecDNA), myeloperoxidase (MPO) and cathelicidin were analyzed in children with febrile UTI caused by E. coli (n = 98, aged 0.3–1.3 years) and in healthy controls (n = 50, 0.5–5.2 years). Moreover, an acute experimental model of UTI was performed on PAD4 knock-out mice with diminished NETs formation (n = 18), and on wild-type mice (n = 15). RESULTS: Children with UTI had significantly higher urinary NETs markers including total ecDNA, nuclear DNA and mitochondrial DNA, altogether with MPO and cathelicidin. The concentrations of MPO and cathelicidin positively correlated with ecDNA (r = 0.53, p ≤ 0.001; r = 0.56, p ≤ 0.001, respectively) and the number of leukocytes in the urine (r = 0.29, p ≤ 0.05; r = 0.27, p ≤ 0.05, respectively). Moreover, urinary MPO was positively associated with cathelicidin (r = 0.61, p ≤ 0.001). In the experimental model, bacterial load in the bladder (20-fold) and kidneys (300-fold) was significantly higher in PAD4 knock-out mice than in wild-type mice. CONCLUSION: Higher urinary NETs makers—ecDNA, MPO and cathelicidin and their correlation with leukocyturia in children with UTI confirmed our hypothesis about the association between NETs and UTI in children. Higher bacterial load in mice with diminished NETs formation suggests that NETs are not only a simple consequence of UTI, but might play a direct role in the prevention of pyelonephritis and other UTI complications. Frontiers Media S.A. 2023-03-20 /pmc/articles/PMC10067609/ /pubmed/37020646 http://dx.doi.org/10.3389/fped.2023.1154139 Text en © 2023 Krivošíková, Šupčíková, Gaál Kovalčíková, Janko, Pastorek, Celec, Podracká and Tóthová. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (https://creativecommons.org/licenses/by/4.0/) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pediatrics
Krivošíková, Katarína
Šupčíková, Nadja
Gaál Kovalčíková, Alexandra
Janko, Jakub
Pastorek, Michal
Celec, Peter
Podracká, Ľudmila
Tóthová, Ľubomíra
Neutrophil extracellular traps in urinary tract infection
title Neutrophil extracellular traps in urinary tract infection
title_full Neutrophil extracellular traps in urinary tract infection
title_fullStr Neutrophil extracellular traps in urinary tract infection
title_full_unstemmed Neutrophil extracellular traps in urinary tract infection
title_short Neutrophil extracellular traps in urinary tract infection
title_sort neutrophil extracellular traps in urinary tract infection
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10067609/
https://www.ncbi.nlm.nih.gov/pubmed/37020646
http://dx.doi.org/10.3389/fped.2023.1154139
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