The role of the human leptomeninges in the inflammatory response to bacterial pathogens

Fowler, Mark Ian (2004) The role of the human leptomeninges in the inflammatory response to bacterial pathogens. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

In the current study, and in vitro model of the human leptomeninges based on the culture based on the culture of meningioma cells, was used to investigate the interactions of the meningeal pathogens Neisseria meningtidis, Escherichia coli K1, Haemophilus influenzae and Streptococcus pneumoniae and the commensal N.lactamica.

All of the meningeal pathogens exhibited a tropism for human meningioma cells. However, there were significant differences between the pathogens in the numbers of bacteria adhering to the cells in vitro. N.meningitidis MC58-7 and E.coli strains DSM and IH3080 adhered to meningioma cell monolayers in the greatest numbers, closely followed by H.influenzae strain RD. N.meningitidis MC58-9 and S.pneumoniae associated with meningioma cells at levels approximately ten-fold lower than those observed with MC58-7 and both E.coli strains, with an additional ten-fold reduction in adherence exhibited by N.lactamica and H.influenzae strain Eagan. Gentamicin-viable counting assays and transmission electron microscopy demonstrated that only E.coli IH3080 could invade meningioma cells. This ability to overcome the barrier properties of the leptomeninges may allow the spread of this particular pathogen into the subpial space and the underlying cerebral tissue and may be associated with the high morbidity and mortality of neonatal meningitis. In addition, the association of meningeal pathogens was investigated with Chang cells as a representative epithelial cell line. The numbers of N.meningtidis MC58-7 and MC58-9 associating with Chang cell monolayers were consistent with those observed with the meningioma cells. However, the levels of association of H.influenzae, E.coli, S.pneumoniae and N.lactamica to Chang cells were approximately 10-20 fold higher than the corresponding values with meningioma cells. The association of meningeal pathogens with a representative epithelial cell line at equally high levels is consistent with the early colonisation of the nasopharynx.