Journal
JOURNAL OF INNATE IMMUNITY
Volume 11, Issue 6, Pages 481-495Publisher
KARGER
DOI: 10.1159/000499342
Keywords
Lactoferrin; Urinary tract infection; Innate immunity; Neutrophil; Urine exosomes; Uropathogenic Escherichia coli
Categories
Funding
- NIH [S10 OD021724, HL107150, HD090259]
- University of California Chancellor's Postdoctoral Fellowship Program
- Hartwell Foundation
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available