Neisseria meningitidis: a traditional extracellular pathogen with an intense intracellular lifestyle

Neisseria meningitidis (meningococcus) is a transitory colonizer of the human nasopharynx that occasionally, for largely unknown reasons, reaches the bloodstream, translocating across the nasopharyngeal mucosa, causing septicemia. The bloodstream spread of bacteria to the meninges can cause meningitis after crossing the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). Thus, the meningococcus must cross several epithelial and endothelial barriers to cause invasive meningococcal disease (IMD). While meningococcal interactions on the surface of epithelial and endothelial cells have been intensively investigated, leading to the identification of key determinants of virulence of this bacterium, relatively little is known about the crossing of the nasopharyngeal epithelial barrier (NEB), the BBB, and BCSFB by the meningococcus. Several mechanisms (transcellular and paracellular) have been proposed, including transcellular crossing and paracellular crossing that might be favored by an epicellular lifestyle of this bacterium. Little is also known about the prevalent (vacuolar or cytoplasmic) localization of N. meningitidis in infected epithelial and endothelial cells and the mechanisms adopted by this microorganism to survive and multiply in the intracellular environment. The purpose of this article is to collect and review what is actually known about the intracellular lifestyle of these microorganisms. The picture that emerges is that although it is traditionally considered an extracellular pathogen (despite its original name, Diplococcus intracellularis meningitidis [Weichseilbaum, 1887]), N. meningitidis engages in complex interactions with host cells in the intracellular microenvironment, involving signal transduction, membrane trafficking, cytoskeleton, metabolic cross-talk, and programmed cell death.