Human Milk Oligosaccharides Protect Bladder Epithelial Cells Against Uropathogenic Escherichia coli Invasion and Cytotoxicity

• Published in: The Journal of infectious diseases Vol. 209; no. 3; pp. 389 - 398
• Main Authors: Lin, Ann E., Autran, Chloe A., Espanola, Sophia D., Bode, Lars, Nizet, Victor
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.02.2014
• Subjects: Apoptosis; Bacteria; Bacterial Adhesion - drug effects; Bacteriology; Biological and medical sciences; Cell death; Cell Survival - drug effects; Endocytosis - drug effects; Epithelial cells; Epithelial Cells - drug effects; Epithelial Cells - microbiology; Focal adhesions; Fundamental and applied biological sciences. Psychology; Health maintenance organizations; Humans; Immunologic Factors - metabolism; Infant; Infections; Infectious diseases; Major and Brief Reports; Medical sciences; Microbiology; Milk, Human - chemistry; Miscellaneous; Oligosaccharides; Oligosaccharides - metabolism; Proteins; Urinary bladder; Uropathogenic Escherichia coli - drug effects; Uropathogenic Escherichia coli - physiology; bladder epithelial cells; apoptosis; human milk oligosaccharides; cell adhesion; uropathogenic; urinary tract infection; Human; Infection; Urinary system; Urinary bladder; Escherichia coli; Bacteria; Epithelial cell; Cytotoxicity; Enterobacteriaceae; Milk; uropathogenic E. coli
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jit464

The invasive pathogen uropathogenic Escherichia coli (UPEC) is the primary cause of urinary tract infections (UTIs). Recurrent infection that can progress to life-threatening renal failure has remained as a serious global health concern in infants. UPEC adheres to and invades bladder epithelial cells to establish infection. Studies have detected the presence of human milk oligosaccharides (HMOs) in urine of breast-fed, but not formulafed, neonates. We investigated the mechanisms HMOs deploy to elicit protection in human bladder epithelial cells infected with UPEC CFT073, a prototypic urosepsis-associated strain. We found a significant reduction in UPEC internalization into HMO-pretreated epithelial cells without observing any significant effect in UPEC binding to these cells. This event coincides with a rapid decrease in host cell cytotoxicity, recognized by LIVE/DEAD staining and cell detachment, but independent of caspase-mediated or mitochondrial-mediated programmed cell death pathways. Further investigation revealed HMOs, and particularly the sialic acid-containing fraction, reduced UPEC-mediated and NF-κB activation. Collectively, our results indicate that HMOs can protect bladder epithelial cells from deleterious cytotoxic and proinflammatory effects of UPEC infection, and may be one contributing mechanism underlying the epidemiológica! evidence of reduced UTI incidence in breast-fed infants.