Figure 1.

Flow chart of the pathogenic triad in bacterial meningitis (BM). (A) Bacterial pathogens adhere to brain microvascular endothelial cells (BMEC) that is the major component of the blood-brain barrier (BBB) and may then transcytotically pass to subendothelial tissues. (B) The nuclear factor-kappaB (NF-κB) is activated by bacterial virulence factors (BV) through their binding to BMEC membrane (CM) receptors (BVR), which can activate the enzyme IκB kinase (IKK) complex (α/β/γ). IKK, in turn, phosphorylates the NF-κB inhibitor IκBα, which results in dissociation of IκBα from NF-κB and eventual degradation of IκBα by the proteosome. The activated NF-κB is then translocated into the nucleus where it cooperatively activates gene transcription with other proteins such as coactivators and RNA polymerases. (C) The sequential steps are shown with numbers. (1), Leukocyte free in circulation and non-adhesive to endothelial cells; (2), Leukocyte tethered to endothelium and rolling under force of blood flow; (3), Leukocyte bound to endothelium and migrating via integrins and intercellular adhesion molecule-1 (ICAM-1); (4), Extravasation of leukocyte from blood vessel with the involvement of junctional adhesion molecule (JAM) and platelet endothelial cell adhesion molecule-1 (PECAM-1); and (5), Leukocyte migrates to source of infection or injury through integrins.