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Inverse relationship between pilus-mediated gonococcal adherence and surface expression of the pilus receptor, CD46
Deborah M Tobiason1, H Steven Seifert1
1Department of Microbiology and Immunology, Northwestern University Medical School, 303 E. Chicago Ave, Searle 6-467, Chicago, IL 60611, USA1.
Abstract:
Pilus-mediated adherence to mucosal epithelial cells is a critical step for Neisseria gonorrhoeae to establish an infection in the human host. CD46, the defined receptor for the gonococcal pilus, is a complement-regulatory protein that is expressed on all human nucleated cells. It was observed that a piliated, Opa(-) variant of gonococcal strain FA1090 adhered with different efficiencies to the human epithelial cell lines tested (Chang, ME180, HEC-1B and PC-3). Surprisingly, these differences in adherence levels did not correlate with levels of CD46 expressed by these cell lines. In fact, there was an inverse relationship between total surface-exposed CD46 and gonococcal adherence. Four major isoforms of CD46 are produced due to alternative RNA splicing of a surface-exposed region and the cytoplasmic tail. The relative isoform surface expression of each cell line was determined, and each was found to express different ratios of the four CD46 isoforms. No correlation could be derived between CD46 isoform surface expression and pilus-mediated gonococcal adherence, indicating that CD46 does not act as a classic receptor for gonococcal pili.
Insights
Neisseria gonorrhoeae uses pili to attach to cells, but CD46 (complement regulatory protein) levels did not predict adherence. Different CD46 isoforms also showed no correlation with gonococcal pilus-mediated cell attachment.
Area of Science:
- Microbiology
- Immunology
- Cell Biology
Background:
- Pilus-mediated adherence is crucial for Neisseria gonorrhoeae infection.
- CD46, a complement-regulatory protein, is expressed on human cells and was previously identified as a gonococcal pilus receptor.
Purpose of the Study:
- To investigate the role of CD46 expression levels and isoforms in Neisseria gonorrhoeae pilus-mediated adherence to human epithelial cells.
Main Methods:
- Assessed pilus-mediated adherence of a gonococcal strain to various human epithelial cell lines.
- Quantified total CD46 surface expression and determined the relative expression of four major CD46 isoforms on these cell lines.
Main Results:
- Gonococcal adherence varied among cell lines despite similar CD46 expression.
- An inverse relationship was observed between total surface CD46 and gonococcal adherence.
- No correlation was found between specific CD46 isoform ratios and adherence levels.
Conclusions:
- CD46 does not function as a classic receptor for Neisseria gonorrhoeae pili.
- Factors beyond CD46 expression influence gonococcal adherence to epithelial cells.