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Meningococcal septic shock is associated with profound vasoplegia, early and severe myocardial dysfunction, and extended skin necrosis responsible for a specific clinical entity designated purpura fulminans (PF). PF represents 90% of fatal meningococcal infections. One characteristic of meningococcal PF is the myocardial dysfunction that occurs in the early phase of sepsis. Furthermore, hemodynamic studies have shown that the prognosis of meningococcal sepsis is directly related to the degree of impairment of cardiac contractility during the initial phase of the disease. To gain insight into a potential interaction of Neisseria meningitidis with the myocardial microvasculature, we modified a previously described humanized mouse model by grafting human myocardial tissue to SCID mice. We then infected the grafted mice with N. meningitides . Using the humanized SCID mouse model, we demonstrated that N. meningitidis targets the human myocardial tissue vasculature, leading to the formation of blood thrombi, infectious vasculitis, and vascular leakage. These results suggest a novel mechanism of myocardial injury in the course of severe N. meningitidis sepsis that is likely to participate in primary myocardial dysfunction.

Following adhesion on brain microvasculature, Neisseria meningitidis is able to cross the blood-brain barrier (BBB) by recruiting the polarity complex and the cell junction proteins, thus allowing the opening of the paracellular route. This feature is the consequence of the activation by the type IV pili of the β 2 -adrenergic receptor/β-arrestin signaling pathway. Here, we have extended this observation to primary peripheral endothelial cells, and we report that the interaction of N. meningitidis with the epithelium is strikingly different. The recruitment of the junctional components by N. meningitidis is indeed restricted to endothelial cell lines, and no alteration of the cell-cell junctions can be seen in epithelial monolayers following meningococcal type IV pilus-mediated colonization. Consistently, the β 2 -adrenergic receptor/β-arrestin pathway was not hijacked by bacteria adhering on epithelial cells. In addition, we showed that the consequences of the bacterial signaling on epithelial cells is different from that of endothelial cells, since N. meningitidis -induced signaling which protects the microcolonies from shear stress on endothelial cells is unable to do so on epithelial cells. Finally, we report that the minor pilin PilV, which has been shown to be essential for endothelial cell response, is not a required bacterial determinant to induce an epithelial cell response. These data demonstrate that even though pilus-mediated signaling induces an apparently similar cortical plaque, in epithelial and endothelial cell lineages, the signaling pathways are strikingly different in both models.