Interactions of Neisseria meningitidis with cells of the human meninges
Abstract
The interaction of Neisseria meningitidis with the meninges that surround and protect the brain is a pivotal event in the progression of bacterial meningitis. Two models of the human meninges were established in vitro, using (i) sections of fresh human brain and (ii) cultures of viable cells grown from human meningiomas. Neisseria meningitidis showed a specific predilection for binding to the leptomeninges and meningeal blood vessels in human brain and not to the cerebral cortex. There was a close correlation between the adherence of different Neisseria species to leptomeninges and cultured cells. The major ligand that mediated adherence was the pilus, and pilin variation modulated the interactions. The presence of Opa protein increased the association of Cap+ meningococci that expressed low-adhesive pili, but did not influence the association of high-adhesive pili. In contrast, Opc did not influence the adherence of Cap+ meningococci, whereas loss of capsule was associated with a more intimate interaction between the bacteria and the meningioma cell that was not apparent with Cap+ meningococci. There was no evidence of internalization of meningococci by meningioma cells in vitro, an observation that is consistent with the barrier properties of the leptomeninges to N. meningitidis observed in vivo.
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All major meningitis causing bacteria can adhere strongly to meningeal fibroblasts and arachnoid barrier-like cells, and Group B Streptococcus bacteria cross the blood brain barrier by binding to vimentin on endothelial cells, which is also highly expressed by arachnoid barrier cells.
“All major meningitis causing bacteria can adhere strongly to meningeal fibroblasts and arachnoid barrier-like cells”
From Living on the Edge of the CNS: Meninges Cell Diversity in Health and Disease (2021) · cites this paper as Hardy et al., 2000
Cites
Schägger, H., & von Jagow, G. (1987) · Analytical Biochemistry · doi:10.1016/0003-2697(87)90587-2 · Cited by 11,420 · see citing works
Hitchcock, P. J., & Brown, T. M. (1983) · Journal of Bacteriology · doi:10.1128/jb.154.1.269-277.1983 · Cited by 1,860 · see citing works
The New WHO Classification of Brain Tumours
Kleihues, P., Burger, P. C., & SCHEITHAUER, B. W. (1993) · Brain Pathology · doi:10.1111/j.1750-3639.1993.tb00752.x · Cited by 1,599 · see citing works
Pathology and genetics of tumours of the nervous system.
Kleihues, P., & Cavennee, W. (2000) · International Agency for Research on Cancer eBooks · Cited by 1,432 · see citing works
Waage, A., Halstensen, A. I., Shalaby, R., Brandtzaeg, P., Kierulf, P., & Espevik, T. (1989) · The Journal of Experimental Medicine · doi:10.1084/jem.170.6.1859 · Cited by 454 · see citing works
Neisseria PilC protein identified as type-4 pilus tip-located adhesin
Rudel, T., Scheuerpflug, I., & Meyer, T. F. (1995) · Nature · doi:10.1038/373357a0 · Cited by 333 · see citing works
Phase variation of gonococcal pili by frameshift mutation in pilC, a novel gene for pilus assembly.
Jonsson, A., Nyberg, G., & Normark, S. J. (1991) · The EMBO Journal · doi:10.1002/j.1460-2075.1991.tb07970.x · Cited by 300 · see citing works
Virji, M., Makepeace, K., Ferguson, D. J. P., & Watt, S. M. (1996) · Molecular Microbiology · doi:10.1046/j.1365-2958.1996.01551.x · Cited by 289 · see citing works
Virji, M., Makepeace, K., Ferguson, D. J. P., Achtman, M., & Moxon, E. R. (1993) · Molecular Microbiology · doi:10.1111/j.1365-2958.1993.tb00922.x · Cited by 263 · see citing works
The Cranial Arachnoid and Pia Mater in Man: Anatomical and Ultrastructural Observations
Alcolado, R., Weller, R. O., Parrish, E. P., & Garrod, D. R. (1988) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.1988.tb00862.x · Cited by 251 · see citing works
Self-citationHaemophilus influenzae Meningitis in Infant Rats after Intranasal Inoculation
Moxon, E. R., Smith, A. L., Averill, D. R., & Smith, D. H. (1974) · The Journal of Infectious Diseases · doi:10.1093/infdis/129.2.154 · Cited by 250 · see citing works
Stimson, E., Virji, M., Makepeace, K., Dell, A., Morris, H. R., Payne, G. D., Saunders, J. R., Jennings, M. P., Barker, S., Panico, M., et al. (1995) · Molecular Microbiology · doi:10.1111/j.1365-2958.1995.mmi_17061201.x · Cited by 250 · see citing works
Virji, M., Watt, S. M., Barker, S., et al. (1996) · Molecular Microbiology · doi:10.1046/j.1365-2958.1996.01548.x · Cited by 246 · see citing works
Antigenic variation of pilin regulates adhesion of Neisseria meningitidis to human epithelial cells
Nassif, X., Lowy, J., Stenberg, P. E., Gaora, P. Ó., Ganji, A., & So, M. (1993) · Molecular Microbiology · doi:10.1111/j.1365-2958.1993.tb01615.x · Cited by 231 · see citing works
(1995) · PubMed · Cited by 222 · see citing works
Nassif, X., Béretti, J., Lowy, J., et al. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.9.3769 · Cited by 218 · see citing works
The role of pili in the interactions of pathogenic Neisseria with cultured human endothelial cells
Virji, M., Käyhty, H. M., Ferguson, D. J. P., Alexandrescu, C., Heckels, J. E., & Moxon, E. R. (1991) · Molecular Microbiology · doi:10.1111/j.1365-2958.1991.tb00807.x · Cited by 207 · see citing works
Self-citationVirji, M., Saunders, J. R., Sims, G., et al. (1993) · Molecular Microbiology · doi:10.1111/j.1365-2958.1993.tb00972.x · Cited by 193 · see citing works
Virji, M., Makepeace, K., Peak, I. R. A., et al. (1995) · Molecular Microbiology · doi:10.1111/j.1365-2958.1995.mmi_18040741.x · Cited by 184 · see citing works
Point mutation in meningococcal por A gene associated with increased endemic disease
McGuinness, B., Clarke, I. N., Lambden, P. R., Barlow, A. K., Heckels, J. E., POOLMAN, J. T., & Jones, D. M. (1991) · The Lancet · doi:10.1016/0140-6736(91)91297-8 · Cited by 171 · see citing works
Self-citationVirji, M., Makepeace, K., Ferguson, D. J. P., et al. (1992) · Molecular Microbiology · doi:10.1111/j.1365-2958.1992.tb01458.x · Cited by 168 · see citing works
The role of neisserial Opa proteins in interactions with host cells
Dehio, C. (1998) · Trends in Microbiology · doi:10.1016/s0966-842x(98)01365-1 · Cited by 162 · see citing works
Glode, M., Sutton, A., Moxon, E. R., et al. (1977) · Infection and Immunity · doi:10.1128/iai.16.1.75-80.1977 · Cited by 144 · see citing works
Weiser, J. N., Goldberg, J. B., Pan, N., et al. (1998) · Infection and Immunity · doi:10.1128/iai.66.9.4263-4267.1998 · Cited by 132 · see citing works
Virji, M., Alexandrescu, C., Ferguson, D. J. P., et al. (1992) · Molecular Microbiology · doi:10.1111/j.1365-2958.1992.tb00848.x · Cited by 127 · see citing works
Vries, F. P. D., ENDE, A. V. D., van Putten, J. P. M., & Dankert, J. (1996) · Infection and Immunity · doi:10.1128/iai.64.8.2998-3006.1996 · Cited by 126 · see citing works
Pathology and Genetics of Tumours of the Nervous System
McComb, R. D. (1998) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199807000-00009 · Cited by 125 · see citing works
Virji, M., & Heckels, J. E. (1986) · Microbiology · doi:10.1099/00221287-132-2-503 · Cited by 124 · see citing works
Self-citationNeisseria meningitidis producing the Opc adhesin binds epithelial cell proteoglycan receptors
Vries, F. P. D., Cole, R. L., Dankert, J., Frosch, M., & van Putten, J. P. M. (1998) · Molecular Microbiology · doi:10.1046/j.1365-2958.1998.00763.x · Cited by 124 · see citing works
Antidesmosomal monoclonal antibody in the diagnosis of intracranial tumours
Parrish, E. P., Steart, P. V., Garrod, D. R., et al. (1987) · The Journal of Pathology · doi:10.1002/path.1711530311 · Cited by 118 · see citing works
Virji, M., Makepeace, K., & Moxon, E. R. (1994) · Molecular Microbiology · doi:10.1111/j.1365-2958.1994.tb01277.x · Cited by 116 · see citing works
PilC of pathogenic Neisseria is associated with the bacterial cell surface
Rahman, M., Källström, H., Normark, S. J., & Jonsson, A. (1997) · Molecular Microbiology · doi:10.1046/j.1365-2958.1997.4601823.x · Cited by 115 · see citing works
Bessen, D. E., & Gotschlich, E. C. (1986) · Infection and Immunity · doi:10.1128/iai.54.1.154-160.1986 · Cited by 107 · see citing works
DeVoe, I. W., & Gilchrist, J. E. (1975) · The Journal of Experimental Medicine · doi:10.1084/jem.141.2.297 · Cited by 101 · see citing works
Brandtzaeg, P., Øvstebø, R., & Kierulf, P. (1992) · The Journal of Infectious Diseases · doi:10.1093/infdis/166.3.650 · Cited by 101 · see citing works
An Ultrastructural and Immunocytochemical Analysis of Leptomeningeal and Meningioma Cultures
Rutka, J. T., Giblin, J. R., Dougherty, D. V., et al. (1986) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-198605000-00012 · Cited by 98 · see citing works
Pili and Outer Membrane Appendages on Neisseria meningitidis in the Cerebrospinal Fluid of an Infant
Stephens, D. S., Edwards, K. M., Morris, F., et al. (1982) · The Journal of Infectious Diseases · doi:10.1093/infdis/146.4.568 · Cited by 94 · see citing works
Stimson, E., Virji, M., Barker, S., Panico, M., Blench, I., Saunders, J. R., Payne, G. D., Moxon, E. R., Dell, A., & Morris, H. R. (1996) · Biochemical Journal · doi:10.1042/bj3160029 · Cited by 88 · see citing works
Achtman, M., Kušećek, B., Morelli, G., et al. (1992) · The Journal of Infectious Diseases · doi:10.1093/infdis/165.1.53 · Cited by 83 · see citing works
Structural comparison of Neisseria gonorrhoeae outer membrane proteins.
Heckels, J. E. (1981) · Journal of Bacteriology · doi:10.1128/jb.145.2.736-742.1981 · Cited by 81 · see citing works
Self-citationTaha, M., Morand, P., Pereira, Y., Eugène, E., Giorgini, D., Larribe, M., & Nassif, X. (1998) · Molecular Microbiology · doi:10.1046/j.1365-2958.1998.00876.x · Cited by 80 · see citing works
Virji, M., & Heckels, J. E. (1983) · Microbiology · doi:10.1099/00221287-129-9-2761 · Cited by 74 · see citing works
Self-citationMarceau, M., Béretti, J., & Nassif, X. (1995) · Molecular Microbiology · doi:10.1111/j.1365-2958.1995.mmi_17050855.x · Cited by 71 · see citing works
Christodoulides, M., McGuinness, B., & Heckels, J. E. (1993) · Journal of General Microbiology · doi:10.1099/00221287-139-8-1729 · Cited by 60 · see citing works
Self-citationBarrier functions of the leptomeninges: a study of normal meninges and meningiomas in tissue culture
FEURER, D. J., & Weller, R. O. (1991) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.1991.tb00739.x · Cited by 56 · see citing works
Self-citationPorat, N., Apicella, M. A., & Blake, M. S. (1995) · Infection and Immunity · doi:10.1128/iai.63.4.1498-1506.1995 · Cited by 54 · see citing works
Jonsson, A. B., Pfeifer, J. D., & Normark, S. J. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.8.3204 · Cited by 52 · see citing works
Porat, N., Apicella, M. A., & Blake, M. S. (1995) · Infection and Immunity · doi:10.1128/iai.63.6.2164-2172.1995 · Cited by 43 · see citing works
Structural and antigenic differences between two types of meningococcal pili
Diaz, J. L., Virji, M., & Heckels, J. E. (1984) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.1984.tb00207.x · Cited by 34 · see citing works
Self-citationPerry, A. C. F., Hart, C. A., Nicolson, I. J., et al. (1987) · Microbiology · doi:10.1099/00221287-133-6-1409 · Cited by 32 · see citing works
Aho, E. L., Botten, J., Hall, R. J., et al. (1997) · Infection and Immunity · doi:10.1128/iai.65.7.2613-2620.1997 · Cited by 32 · see citing works
Cytokeratin provides a specific marker for human arachnoid cells grown in vitro
FRANK, E. H., Burge, B. W., Liwnicz, B. H., et al. (1983) · Experimental Cell Research · doi:10.1016/0014-4827(83)90138-6 · Cited by 27 · see citing works
Age-Related Susceptibility to Haemophilus influenzae Type b Disease in Rabbits
Schneerson, R., & Robbins, J. B. (1971) · Infection and Immunity · doi:10.1128/iai.4.4.397-401.1971 · Cited by 27 · see citing works
del Rı́o, C., Stephens, D. S., Knapp, J. S., et al. (1989) · Journal of Clinical Microbiology · doi:10.1128/jcm.27.5.1045-1049.1989 · Cited by 21 · see citing works
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“7c) [5, 9, 34, 39], although the nature of the bacterial ligands and meningeal cell receptors has not been explored extensively.”
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- Authors
- Hardy, S. J., Christodoulides, M., Weller, R. O., & Heckels, J. E.
- Affiliations
- Southampton General Hospital (GB)
- Corresponding author
- Christodoulides, Myron
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2000-05
- Volume
- 36
- Issue
- 4
- Pages
- 817-829
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- OpenAlex
- W2060390877
- Cited by
- 78
- References
- 54
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 4 · 2015: 6 · 2014: 3 · 2013: 3 · 2012: 5
- FWCI
- 2.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Funders
- University of Liverpool
- Medical Research Council
- Topics
- Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
- Life Sciences › Immunology and Microbiology › Microbiology › Microbial infections and disease research
- Keywords
- Neisseria meningitidis, bacterial meningitis, leptomeninges, Opa proteins, meningeal blood vessels, bacterial internalization, host-pathogen interaction
- MeSH terms
- Animals, Bacterial Adhesion, Brain, Humans, Meninges, Meningioma, Neisseria meningitidis, Species Specificity, Tumor Cells, Cultured, Microscopy, Confocal, Mice
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