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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.<\/jats:p>","DOI":"10.1084\/jem.20031159","type":"journal-article","created":{"date-parts":[[2003,11,3]],"date-time":"2003-11-03T22:23:02Z","timestamp":1067898182000},"page":"1313-1322","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":43,"title":["Down-regulation of CD46 by Piliated <i>Neisseria gonorrhoeae <\/i>"],"prefix":"10.1084","volume":"198","author":[{"given":"Darcy B.","family":"Gill","sequence":"first","affiliation":[{"name":"1Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Koomey","sequence":"additional","affiliation":[{"name":"2Centre for Molecular Biology and Neuroscience, Biotechnology Centre of Oslo"},{"name":"3Department of Microbiology, Institute of Pharmacy, University of Oslo, 0316 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janne G.","family":"Cannon","sequence":"additional","affiliation":[{"name":"4Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Atkinson","sequence":"additional","affiliation":[{"name":"1Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2003,11,3]]},"reference":[{"key":"2023072512181463000_BIB1","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/S0952-7915(99)00049-7","volume":"12","year":"2000","journal-title":"Curr. 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