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CD46 (Membrane Cofactor Protein) Acts as a Human Epithelial Cell Receptor for Internalization of Opsonized Uropathogenic Escherichia coli

Lookup NU author(s): Professor Neil SheerinORCiD

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Abstract

Escherichia coli is a common urinary pathogen whose uptake into epithelial cells is mediated by attachment through type 1 fimbriae. In this study, we show by using using human urinary tract epithelial cells that maximal internalization of E. coli is achieved only when bacteria are opsonized with complement. The concentrations of complement proteins in the urine rise sufficiently during infection to allow bacterial opsonization. The complement regulatory protein, CD46 (membrane cofactor protein), acts in cohort with fimbrial adhesion to promote the uptake of pathogenic E. coli. This uptake is inhibited by RNA interference to lower the expression of CD46 and by soluble CD46 that will competitively inhibit opsonized bacteria binding to cell surface CD46. We propose that efficient internalization of uropathogenic E. coli by the human urinary tract depends on cooperation between fimbrial-mediated adhesion and C3 receptor (CD46)-ligand interaction. Complement receptor-ligand interaction could pose a new target for interrupting the cycle of reinfection due to intracellular bacteria.


Publication metadata

Author(s): Li K, Feito MJ, Sacks SH, Sheerin NS

Publication type: Article

Publication status: Published

Journal: Journal of Immunology

Year: 2006

Volume: 177

Issue: 4

Pages: 2543-2551

ISSN (print): 0022-1767

ISSN (electronic): 1550-6606

Publisher: American Association of Immunologists

URL: http://www.jimmunol.org/cgi/content/abstract/177/4/2543


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