Down-regulation of CD46 by piliated Neisseria gonorrhoeae

Area of Science:

• Microbiology
• Immunology
• Cell Biology

Background:

• Human membrane cofactor protein (CD46) is crucial for host defense against complement-mediated attack.
• CD46 may serve as a receptor for pathogenic Neisseria species, including Neisseria gonorrhoeae.
• Understanding host-pathogen interactions is vital for developing effective treatments.

Purpose of the Study:

• To investigate the effect of Neisseria gonorrhoeae on CD46 expression in human cervical cells.
• To elucidate the mechanism by which Neisseria gonorrhoeae alters CD46 surface levels.
• To determine the role of bacterial pili in CD46 modulation.

Main Methods:

• Exposure of the human cervical cell line ME-180 to piliated and nonpiliated Neisseria gonorrhoeae.
• Quantification of CD46 surface expression using flow cytometry.
• Analysis of CD46 shedding into cell supernatants.
• Investigation of the role of the pilus retraction protein PilT.

Main Results:

• Piliated Neisseria gonorrhoeae significantly reduced CD46 surface expression on ME-180 cells by up to 80% within 6 hours, an effect lasting at least 24 hours.
• CD46 down-regulation was mediated by shedding of the protein into the supernatant, not by intracellular retention or inhibition of protein synthesis.
• Gonococci lacking the PilT protein failed to down-regulate CD46, but restoring PilT expression re-established this effect.
• Experimental infection of human volunteers showed that gonococcal variants initially incapable of CD46 down-regulation acquired this ability upon re-isolation.

Conclusions:

• Neisseria gonorrhoeae actively manipulates the host cell environment by shedding CD46.
• Pilus-mediated interaction is essential for this pathogen-induced down-regulation of CD46.
• This mechanism represents a novel strategy employed by Neisseria gonorrhoeae to evade host defenses.