Urothelial CD44 facilitates Escherichia coli infection of the murine urinary tract.
Escherichia coli is the most common pathogen found in urinary tract infections (UTIs), mainly affecting children and women. We report that CD44, a hyaluronic acid (HA) binding protein that mediates cell-cell and cell-matrix interactions, facilitates the interaction of E. coli with urothelial cells and thus the infection of the host. We found that CD44 is constitutively expressed on urothelial cells and that HA accumulates in E. coli-induced UTI. In CD44-deficient mice, the bacterial outgrowth was dramatically less compared with wild-type mice despite similar granulocyte influx in the bladder and in the kidney as well as comparable cytokines/chemokines levels in both genotypes. E. coli was able to bind HA, which adhered to CD44-positive tubular epithelial cells. Most importantly, the interaction of CD44 on tubular epithelial cells with HA facilitated the migration of E. coli through the epithelial monolayer. The results provide evidence that CD44 on urothelial cells facilitates E. coli UTI. Disruption of the interaction between CD44 and HA in the bladder may provide a new approach to prevent and to treat UTI.
Rouschop
Kasper M A
KM
Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Kasper.Rouschop@maastro.unimaas.nl
Sylva
Marc
M
Teske
Gwendoline J D
GJ
Hoedemaeker
Inge
I
Pals
Steven T
ST
Weening
Jan J
JJ
van der Poll
Tom
T
Florquin
Sandrine
S
D000818:Animals; D001422:Bacterial Adhesion / Q000276:immunology; D018988:Bacterial Translocation / Q000276:immunology; D018925:Chemokines / Q000096:biosynthesis; D015169:Colony Count, Microbial; D016207:Cytokines / Q000096:biosynthesis; D004927:Escherichia coli Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D005260:Female; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006820:Hyaluronic Acid / Q000502:physiology; D018836:Inflammation Mediators / Q000378:metabolism; D007684:Kidney Tubules / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000235:genetics / Q000276:immunology; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology; D014552:Urinary Tract Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D019459:Urothelium / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
D018925:Chemokines; D016207:Cytokines; D018960:Hyaluronan Receptors; D018836:Inflammation Mediators; D006820:Hyaluronic Acid