The Core Lipopolysaccharide ofEscherichia coliIs a Ligand for the Dendritic-Cell-Specific Intercellular Adhesion Molecule Nonintegrin CD209 Receptor

Abstract

The dendritic-cell-specific intercellular adhesion molecule nonintegrin (DC-SIGN) CD209 is a receptor for Escherichia coli K-12 that promotes bacterial adherence and phagocytosis. However, the ligand of E. coli for DC-SIGN has not yet been identified. In this study, we found that DC-SIGN did not mediate the phagocytosis of several pathogenic strains of E. coli, including enteropathogenic E. coli, enterohemorrhagic E. coli, enterotoxigenic E. coli, and uropathogenic E. coli, in dendritic cells or HeLa cells expressing human DC-SIGN antigen. However, we showed that an outer core lipopolysaccharide (LPS) (rough) mutant, unlike an inner core LPS (deep rough) mutant or O-antigen-expressing recombinant of E. coli K-12 was phagocytosed. These results demonstrate that the host cells expressing DC-SIGN can phagocytose E. coli in part by interacting with the complete core region of the LPS molecule. These results provide a mechanism for how O antigen acts as an antiphagocytic factor.

Role of N-Acetylglucosamine within Core Lipopolysaccharide of Several Species of Gram-Negative Bacteria in Targeting the DC-SIGN (CD209)

“…1) The core LPS of E. coli mediates the interaction with DC-SIGN. Our previous data (13) and Fig. 3 confirm that the waaR mutant does not interact with DC-SIGN as well as its parent strain CS180, suggesting that it is the core LPS rather than other components on the E. coli surfaces interacting with DC-SIGN.…”

“…1) from Neisseria gonorrhoeae (GC) in both DCs and HeLa cells expressing human DC-SIGN Ag (HeLa-DC-SIGN) (12). We further demonstrated that it is the core LPS region of E. coli that interacts with DC-SIGN (13).…”

“…However, we did not observe significant morphological changes, such as changes of cell shape and/or detachment of HeLa cells from plates after 2.5 h of incubation with these two bacterial strains. In addition, the results from CS1861/CS180 and GR-12/SMB-316 presented here were regarded as controls because similar data were published (13).…”

“…We recently demonstrated that core LPS from E. coli is a ligand for DC-SIGN by showing that some rough strains of K-12 and uropathogenic E. coli, but not their isogenic smooth derivatives, interact with HeLa cells expressing DC-SIGN (HeLa-DC-SIGN) (13). We were subsequently interested in determining whether rough variants of other E. coli strains were able to interact with DC-SIGN.…”

“…To determine whether GlcNAc-containing oligosaccharides would inhibit the core-LPS-DC-SIGN interaction, four oligosaccharides (GlcNAc-Gal-Glc, Gal-GlcNAc, Fuc-GlcNAc, and GlcNAc-Gal-OMe), two single sugar residues (GlcNAc and GalNAc), and one sugar compound (glucan) were tested. Mannan, which inhibits core-LPS-DC-SIGN interaction as shown previously (12,13), was used as a positive control for inhibition. Fig.…”