Interactions of Neisseria meningitidis with cells of the human meninges

Abstract

SummaryThe 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 1 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 1 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 1 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.

Differential Gene Expression during Meningeal-Meningococcal Interaction: Evidence for Self-Defense and Early Release of Cytokines and Chemokines

“…The epithelial origin of the cultured cells was confirmed with the detection of the epithelial membrane antigen and desmoplakins I and II (13,19) by fluorescence microscopy (data not shown). Meningiomas of passage 5 were grown to confluence in two separate 175-cm 2 tissue culture flasks (Nunc) using Dulbecco's modified Eagle medium (DMEM; GIBCO, Paisley, United Kingdom) supplemented with 10% fetal calf serum and 1% antibiotic-antimycotic (GIBCO).…”

“…Human meningothelial cells, obtained from surgically removed tumors of several patients, were isolated and cultured using a method based on that described by Hardy et al (19). The epithelial origin of the cultured cells was confirmed with the detection of the epithelial membrane antigen and desmoplakins I and II (13,19) by fluorescence microscopy (data not shown).…”

“…Meningiomas are benign epithelial meningeal tumors that arise from arachnoidal meningothelial cells and have been demonstrated as a suitable model for N. meningitidis interactions (19). Pilus-mediated adherence to a meningioma monolayer has been shown, but there was no evidence of invasion (19).…”

“…Pilus-mediated adherence to a meningioma monolayer has been shown, but there was no evidence of invasion (19). In this study we used cDNA expression arrays to identify early differential gene expression induced by meningococcal challenge, focusing on whether meninges-derived human cells may be a source of the cytokines detected in CSF during meningitis.…”

Interaction ofNeisseria meningitidiswith Human Meningeal Cells Induces the Secretion of a Distinct Group of Chemotactic, Proinflammatory, and Growth-Factor Cytokines

“…In addition, in vitro models based on primary cultures of cells from the leptomeninges are not possible (9). Recently, we have established an in vitro model based on culture of cells from benign tumors (meningiomas) of the human meninges; these cells have essentially the same profile of cell markers as normal leptomeningeal cells and show identical patterns of reactivity with meningococci (17). However, little is known about the role of the leptomeninges in initiating and sustaining the intracranial inflammatory response and the potential contributions of individual meningococcal components to cytokine induction.…”