The Journal of Experimental Medicine
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Published 3 November 2003. doi:10.1084/jem.20031159
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© Rockefeller University Press, 0022-1007/2003/11/1313 $5.00
The Journal of Experimental Medicine, Volume 198, Number 9, 1313-1322

Down-regulation of CD46 by Piliated Neisseria gonorrhoeae

Darcy B. Gill1, Michael Koomey2,3, Janne G. Cannon4 and John P. Atkinson1

1 Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110
2 Centre for Molecular Biology and Neuroscience, Biotechnology Centre of Oslo
3 Department of Microbiology, Institute of Pharmacy, University of Oslo, 0316 Oslo, Norway
4 Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599

Address correspondence to John P. Atkinson, Washington University School of Medicine, Campus Box 8045, 660 S. Euclid, St. Louis, MO 63110. Phone: (314) 362-8391; Fax: (314) 362-1366; email: jatkinso{at}im.wustl.edu

Human membrane cofactor protein (CD46) protects host cells against complement attack and may function as a receptor for pathogenic Neisseriae. We assessed CD46 expression in the human cervical cell line ME-180 after exposure to Neisseria gonorrhoeae. Piliated but not nonpiliated gonococci adhered to cells and produced up to an 80% reduction in CD46 surface expression by 6 h that persisted for at least 24 h. This response required a minimum multiplicity of infection of 10 and was not prevented by antibodies to CD46. CD46 down-regulation was not attributable to intracellular retention or a global or specific shutdown of mRNA or protein synthesis. Substantial quantities of CD46 were found in the supernatants, indicating a specific shedding of this protein. Adherent gonococci lacking the pilus retraction protein PilT did not down-regulate CD46 but de-repression of pilT expression restored CD46 down-regulation. After experimental infection of human volunteers with a gonococcal variant incapable of inducing CD46 down-regulation, variants of this strain were reisolated that exhibited CD46 down-regulation. Pilus-mediated interactions of gonococci with human epithelial cells results in a pathogen-induced manipulation of the host cell environment in which a membrane protein is removed from epithelial cells by liberation into the surrounding milieu.

Key Words: Type IV pilus • PilT • pilus retraction • PilE • protein shedding


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