Abstract
Infection of mucosal surfaces by N. gonorrhoeae and N. meningitidis may result in inflammation indicating potential injury to host cells. We used human fallopian tube organ cultures (FTOC) and human nasopharyngeal organ cultures (NPOC) to study the mechanisms by which gonococci and meningococci damage human mucosal surfaces. Early in the course of FTOC infected with gonococci and NPOC infected with meningococci, damage was most apparent to ciliary activity. Loss of ciliary activity was accompanied by sloughing of ciliated cells. The damage to ciliated cells was not associated with attachment of gonococci or meningococci to these cells or the presence of organisms within ciliated cells. Infection with the commensal N. subflava did not result in significant damage to human FTOC or NPOC ciliary activity. LPS appears to be a major toxin of gonococci for human FTOC ciliated cells. Gonococcal peptidoglycan fragments also damage FTOC ciliary activity. Both piliated (P+) and nonpiliated (P-) gonococci and meningococci damage FTOC and NPOC ciliary activity, but P+ organisms damage ciliary activity more rapidly than P- organisms. Damage to FTOC ciliated cells was produced by <10 μg/ml of purified gonococcal and meningococcal LPS. By 1–2h after exposure to LPS, vesicles containing LPS were distributed throughout the cytoplasm of ciliated cells. Polymyxin B neutralized LPS-induced damage, suggesting that the lipid A portion of LPS was the toxic moiety. In contrast, purified gonococcal and meningococcal LPS at 100 μg/ml did not damage human NPOC or FTOC from rabbits, pigs and cows. These studies indicate that N. gonorrhoeae and possibly N. meningitidis damage ciliated epithelial celsl indirectly by release of toxins from the organisms. The differences in susceptibility of FTOC and NPOC to LPS may suggest changes in density of receptors for LPS and may help explain variation in severity of gonococcal and meningococcal interactions at different human mucosal surfaces.
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Cooper, M. D., Z. A. McGee, M. H. Mulks, J. M. Koomey & T. L. Hindman (1984) Attachment to and invasion of human fallopian tube mucosa by an IgA1 protease-deficient mutant of Neisseria gonorrhoeae and its wild-type parent. J. Infect. Dis. 150: 737–744
Cooper, M. D., P. A. McGraw & M. A. Melly (1986) Localization of gonococcal lipopolysaccharide and its relationship to toxic damage in human fallopian tube mucosa. Infect. Immun. 51: 425–430
Farley, M. M., D. S. Stephens, M. H. Mulks, M. D. Cooper, J. V. Bricker, S. S. Mirra & A. Wright (1986) Pathogenesis of IgA1 protease producing and nonproducing Haemophilus influenzae in human nasopharyngeal organ cultures. J. Infect Dis. 154: 752–759
Goldman, W. E., D. G. Klapper, J. B. Baseman (1982) Detection, isolation and analysis of a released Bordetella pertussis product toxic to cultured tracheal cells. Infect. Immun. 36: 782–794
Gregg, C. R., M. A. Melly C. G. Hellerquist, J. G. Coniglio & Z. A. McGee (1981a) Toxic activity of purified lipopolysaccharide of Neisseria gonorrhoeae for human fallopian tube mucosa. J. Infect. Dis. 143: 432–439
Gregg, C. R., M. P. Johnson, D. Taylor-Robinson, M. A. Melly & A. Z. McGee (1981b) Host species-specific damage to oviduct mucosa by Neisseria gonorrhoeae lipopolysaccharide. Infect. and Immun. 34: 1056–1058
Johnson, A. P., Z. A. McGee, P. H. Argabrite, M. A. Melly & D. Taylor-Robinson (1980) Selectivity for human genital mucosa of a toxic factor elaborated by Neisseria gonorrhoeae. FEMS Microbiology Lett. 8: 29–31
McGee, Z. A., A. P. Johnson & D. Taylor-Robinson (1976) Human fallopian tubes in organ culture: preparation, maintenance and quantitation of damage by pathogenic microorganisms. Infect. Immun. 13: 608–618
McGee, Z. A. A. P. Johnson & D. Taylor-Robinson (1981) Pathogenic mechanisms of Neisseria gonorrohoeae: observations on damage to human fallopian tubes in organ culture by gonococci of colony type 1 or type 4. J. Infect. Dis. 143: 413–422
McGee, Z. A., M. A. Melly, C. R. Gregg, R. C. Horn D. Taylor-Robinson, A.P. Johnson & J. A. McCutchan (1978) Virulence factors of gonococci: studies using human fallopian tube organ cultures. Immunobiology of Neisseria gonorrhoeae. American Society for Microbiology, Washington, D.C.
McGee, Z. A., D. S. Stephens, L. H. Hoffman, W. F.III Sehlech & R. G. Horn (1983) Mechanisms of mucosal invasion by pathogenic Neisseria. Rev. Infect. Dis. 5: S708–714
Mc Gee, Z. A., D. S. Stephens, M. A. Melly, C. R. Gregg, W. F.III Schlech & L. H. Hoffman (1982) The role of attachment in the pathogenisis of disease caused by Neisseria gonorrhoeae and Neisseria meningitidis. In: D. Schlessinger (Ed) Microbiology (pp. 292–295). Amer. Soc. for Microbiol, Washington, D.C.
Melly, M. A., C. R. Gregg & Z. A. McGee (1981) Studies of toxicity of Neisseria gonorrhoeae for human fallopian tuber mucosa. J. Infect. Dis. 143: 423–431
Melly, M. A., Z. A. McGee & R. S. Rosenthal (1984) Ability of monomeric peptidoglycan fragments from Neisseria gonorrhoea to damage human fallopian-tube mucosa. J. Infect. Dis. 149: 378–386.
Stephens, D. S., L. H. Hoffman & Z. A. McGee (1983) Interaction of Neisseria meningitidis with human nasopharyngeal mucosa: attachment and entry into columar epithelial cells. J. Infect. Dis. 148: 369–376
Stephens, D. S., Z. A. McGee, M. A. Hoffman & C. R. Gregg (1982) Attachment of pathogenic Neisseria to human mucosal surfaces: role in pathogenesis. Infection 10: 192–195.
Stephens, D. S. & Z. A. McGee (1981) Attachment of Neisseria meningitidis to human mucosal surfaces: influence of pili and type of receptor cell. J. Infect. Dis. 143: 525–532
Stephens, D. S., A. M. Whitney, M. A. Melly, L. H. Hoffman, M. M. Farley & C. E. Frasch (1986) Analysis of damage to human ciliated nasopharyngeal epithelium by Neisseria meningitidis. Infect. Immun. 51: 579–585
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Stephens, D.S., McGee, Z.A. & Cooper, M.D. Cytopathic effects of the pathogenic Neisseria. Studies using human fallopian tube organ cultures and human nasopharyngeal organ cultures. Antonie van Leeuwenhoek 53, 575–584 (1987). https://doi.org/10.1007/BF00415519
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DOI: https://doi.org/10.1007/BF00415519