Pertussis toxin transiently affects barrier integrity, organelle organization and transmigration of monocytes in a human brain microvascular endothelial cell barrier model

Abstract

SummaryEncephalopathies and neurological disorders are sometimes associated with respiratory tract infections caused by Bordetella pertussis. For these complications to occur cerebral barriers have to be compromised. Therefore, the influence of pertussis toxin (PT), a decisive virulence determinant of B. pertussis, on endothelial barrier integrity was investigated. Human brain microvascular endothelial cells cultured on Transwell filter devices were used as model for the blood brain barrier. PT, but not its B-oligomer, induced a reduction of the transendothelial resistance and enhanced the permeability for the protein marker horseradish peroxidase. Moreover, transmigration of human monocytes was also elevated suggesting a PT-associated enhancement of the diapedesis of blood leucocytes. Uptake and trafficking of PT was followed by electron microscopy via clathrin-coated pits and accumulation in lysosomes and microvesicular bodies. The breach in barrier integrity was accompanied by a transient disintegration of Golgi structures. Interestingly, PT-induced effects were only transient and restoration of barrier function was observed after 24 h. In summary, intoxication by PT causes a transient destruction of the cellular organization in human brain-derived endothelial cells resulting in a transient disruption of barrier functions. We suggest that these findings reflect early steps in the development of neurological disorders associated with pertussis disease.

Central histamine H3receptor signaling negatively regulates susceptibility to autoimmune inflammatory disease of the CNS

“…Induction of EAE by active immunization with MOG and adjuvants obviously involves a peripheral initiation phase. Two components of this immunization are CFA and PTX, both of which are known to increase BBB permeability (33)(34)(35)(36) and cytokine and inflammatory mediator levels within the CNS rapidly after injection. Specifically, either CFA or PTX can elicit IL-1␤, TNF-␣, and/or IL-6 production in the CNS within 2 h after their injection (37)(38)(39)(40)(41)(42).…”

Glycosphingolipids in vascular endothelial cells: relationship of heterogeneity in Gb3Cer/CD77 receptor expression with differential Shiga toxin 1 cytotoxicity

“…HBMECs, which form the barrier that protects the brain from microbes and toxins circulating in the blood [19,20], have been employed in numerous studies as target cells for pathogen invasion [21,22], fimbriae-mediated bacterial interactions [23], and bacterial toxins [24,25]. EA.…”

Pertussis Toxin Exploits Specific Host Cell Signaling Pathways for Promoting Invasion and Translocation of Escherichia coli K1 RS218 in Human Brain-derived Microvascular Endothelial Cells

“…It has been shown in several studies that pertussis toxin (PTx), 2 a decisive and secreted virulence factor of B. pertussis, affects cerebral vascular barriers and transiently increases the permeability of the blood-brain barrier (1,(3)(4)(5)(6)(7)(8). PTx belongs to the class of AB toxins with a catalytically active monomeric A-subunit, which transfers ADP-ribose from NAD to a cysteine residue of G i proteins (9,10).…”