Lin AE, Autran CA, Espanola SD, Bode L, Nizet V. (2014) Human Milk Oligosaccharides Protect Bladder Epithelial Cells Against Uropathogenic Escherichia coli Invasion and Cytotoxicity. J Infect Dis. 209(3):323-4. PMID: 23990566 PMCID: PMC3883170.
The invasive pathogen Uropathogenic E. coli (UPEC) is the primary cause of urinary tract infections (UTI). 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 (HMO) in urine of breast-fed, but not formula-fed neonates. We investigated the mechanisms HMO 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 HMO, and particularly the sialic acid-containing fraction, reduced UPEC-mediated MAPK and NF-κB activation. Collectively, our results indicate that HMO can protect bladder epithelial cells from deleterious cytotoxic and pro-inflammatory effects of UPEC infection, and may be one contributing mechanism underlying the epidemiological evidence of reduced UTI incidence in breast-fed infants.
apoptosis; bladder epithelial cells; cell adhesion; human milk oligosaccharides; urinary tract infection; uropathogenic E. coli
Link to journal: http://jid.oxfordjournals.org/