Inverse relationship between pilus-mediated gonococcal adherence and surface expression of the pilus receptor, CD46

Pilus-mediated adherence to mucosal epithelial cells is a critical step for Neisseria gonorrhoeae to establish an infection in the human host. CD46, t he defined receptor for the gonococcal pilus, is a complement-regulatory pr otein that is expressed on all human nucleated cells. It was observed that a piliated, Opa(-) variant of gonococcal strain FA1090 adhered with differe nt efficiencies to the human epithelial cell lines tested (Chang, ME180, HE C-1B and PC-3). Surprisingly, these differences in adherence levels did not correlate with levels of CD46 expressed by these cell lines. In fact, ther e was an inverse relationship between total surface-exposed CD46 and gonoco ccal adherence. Four major isoforms of CD46 are produced due to alternative RNA splicing of a surface-exposed region and the cytoplasmic tall. The rel ative isoform surface expression of each cell line was determined, and each was found to express different ratios of the four CD46 isoforms. No correl ation could be derived between CD46 isoform surface expression and pilus-me diated gonococcal adherence, indicating that CD46 does not act as a classic receptor for gonococcal pili.