Augmentation of Urinary Lactoferrin Enhances Host Innate Immune Clearance of Uropathogenic Escherichia coli.
Animals
Disease Models, Animal
Escherichia coli Infections
/ immunology
Exosomes
/ metabolism
Extracellular Traps
/ metabolism
Female
Humans
Immunity, Innate
Immunocompromised Host
Iron
/ metabolism
Lactoferrin
/ urine
Mice
Mice, Inbred C57BL
Mice, Knockout
Neutrophils
/ immunology
Urinary Bladder
/ immunology
Urinary Tract Infections
/ immunology
Uropathogenic Escherichia coli
/ physiology
Innate immunity
Lactoferrin
Neutrophil
Urinary tract infection
Urine exosomes
Uropathogenic Escherichia coli
Journal
Journal of innate immunity
ISSN: 1662-8128
Titre abrégé: J Innate Immun
Pays: Switzerland
ID NLM: 101469471
Informations de publication
Date de publication:
2019
2019
Historique:
received:
12
12
2018
accepted:
26
02
2019
pubmed:
6
5
2019
medline:
3
7
2020
entrez:
6
5
2019
Statut:
ppublish
Résumé
Urinary tract infection (UTI) is a prominent global health care burden. Although UTI is readily treated with antibiotics in healthy adults, complicated cases in immune-compromised individuals and the emerging antibiotic resistance of several uropathogens have accelerated the need for new treatment strategies. Here, we surveyed the composition of urinary exosomes in a mouse model of uropathgenic Escherichia coli (UPEC) UTI to identify specific urinary tract defense constituents for therapeutic development. We found an enrichment of the iron-binding glycoprotein lactoferrin in the urinary exosomes of infected mice. In subsequent in vitro studies, we identified human bladder epithelial cells as a source of lactoferrin during UPEC infection. We further established that exogenous treatment with human lactoferrin (hLf) reduces UPEC epithelial adherence and enhances neutrophil antimicrobial functions including bacterial killing and extracellular trap production. Notably, a single intravesicular dose of hLf drastically reduced bladder bacterial burden and neutrophil infiltration in our murine UTI model. We propose that lactoferrin is an important modulator of innate immune responses in the urinary tract and has potential application in novel therapeutic design for UTI.
Identifiants
pubmed: 31055580
pii: 000499342
doi: 10.1159/000499342
pmc: PMC6758950
doi:
Substances chimiques
Iron
E1UOL152H7
Lactoferrin
EC 3.4.21.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
481-495Subventions
Organisme : NICHD NIH HHS
ID : P50 HD090259
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI052453
Pays : United States
Organisme : NIH HHS
ID : S10 OD021724
Pays : United States
Informations de copyright
© 2019 The Author(s) Published by S. Karger AG, Basel.
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