Interaction of Neisseria meningitidis with cells of the human meninges

Abstract

A model was established to study the interactions of Neisseria meningitidis with meningioma cells. A panel of meningococcal phenotypic variants was selected from the pathogenic strains MC58 and MC59 which differed in their pilus, Opa and Opc expression. All bacteria were encapsulated and of the same LPS immunotype, although an acapsulate mutant was included as a comparison. Meningioma cells were cultured and infected with these meningococci. Total bacterial association was determined by viable counting, and internalisation was determined by pre-incubation with gentamicin. Meningococcal association with meningioma cells was also visualised by scanning and transmission electron microscopy and by confocal microscopy.

The adherence of encapsulated meningococci to human meningioma cells was predominantly pilus-mediated and subject to antigenic variation of the pilin subunit. In organisms with less adherent pili, the presence of Opa protein did increase adherence slightly, but Opc had no effect. Experimental evidence suggests that meningococci do not invade meningioma cells.

The work described in this thesis has established an in vitro model for studying the interactions of Neisseria meningitidis with cells of the human meninges which will can be used for further studies including receptor-mediated adhesion of meningococci to the meninges, and the production of pro-inflammatory cytokines and chemokines in the inflammatory response of meningitis. A greater understanding of these mechanisms may highlight possible avenues for therapeutic strategies to alleviate the sequelae associated with meningococcal meningitis.

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