CD46 (membrane cofactor protein) acts as a human epithelial cell receptor for internalization of opsonized uropathogenic Escherichia coli

K Li, MJ Feito, SH Sacks, NS Sheerin - The Journal of Immunology, 2006 - journals.aai.org
The Journal of Immunology, 2006journals.aai.org
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 …
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.
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