DC-SIGN (CD209) recognition of Neisseria gonorrhoeae is circumvented by lipooligosaccharide variation.

Neisseria gonorrhoeae (GC) or Escherichia coli HB101 (hereafter referred to as E. coli) expressing opacity (Opa) proteins adhere to human host cells and stimulate phagocytosis as a result of the interaction of certain Opa proteins to carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1; CD66a) receptors. Our experiments show that the Opa-CEACAM1 interaction does not play a significant role in adherence between these bacteria and dendritic cells (DCs). Instead, phagocytosis of GC and E. coli by DCs is mediated by the DC-specific intercellular adhesion molecule-grabbing nonintegrin, (SIGN; CD209) receptor. DC-SIGN recognition and subsequent phagocytosis of GC are limited, however, to a lipooligosaccharide (LOS) mutant (lgtB) of GC. This conclusion is supported by experiments demonstrating that HeLa cells expressing human DC-SIGN (HeLa-DC-SIGN) bind exclusively to and engulf an lgtB mutant of GC, and this interaction is blocked specifically by an anti-DC-SIGN antibody. The experiments suggest that LOS variation may have evolved as a mechanism for GC to avoid phagocytosis by DCs.