Pathogenesis of meningococcemia

Abstract

Neisseria meningitidis is responsible for two major diseases: cerebrospinal meningitis and/or septicemia. The latter can lead to a purpura fulminans, an often-fatal condition owing to the associated septic shock. These two clinical aspects of the meningococcal infection are consequences of a tight interaction of meningococci with host endothelial cells. This interaction, mediated by the type IV pili, is responsible for the formation of microcolonies on the apical surface of the cells. This interaction is followed by the activation of signaling pathways in the host cells leading to the formation of a microbiological synapse. A low level of bacteremia is likely to favor the colonization of brain vessels, leading to bacterial meningitis, whereas the colonization of a large number of vessels by a high number of bacteria is responsible for one of the most severe forms of septic shock observed.

Figure 1.

Interaction of Neisseria meningitidis with endothelial cells. N. meningitidis adhere to brain microvascular endothelial cells through an interaction between type IV pili and an unknown adhesion receptor (Nassif et al. 1994). Following initial bacterial adhesion, type IV pili mediate the recruitment and the activation of the β2-adrenoceptor thus leading to the organization of a specific cytoplasmic molecular complex, referred to as cortical plaques. The formation of cortical plaques results (1) from the local accumulation of ezrin and ezrin-binding proteins, and (2) from the accumulation of β-arrestins and β-arrestin-binding molecules such as Src, which induce active actin polymerization, and that of the junctional proteins p120-catenin and VE-cadherin (Hoffmann et al. 2001; Coureuil et al. 2009, 2010). Consequently, this promotes the opening of the cell–cell junctions and allows the transmigration of bacteria through the endothelium.

Figure 2.

The clinical features of meningococcemia are dependent on bacterial load. A low level of bacteremia is likely to be associated with limited vascular colonization and few purpuric lesions. Some colonies in the brain capillaries may breach the blood–brain barrier and proliferate into the central nervous system (CNS). Thus, few colonies are sufficient to induce meningitis. On the other hand, high bacteremia is associated with an important colonization of the peripheral blood vessels that results in a fast and strong vascular leakage.