Blood vessel-associated inflammatory microglia and astrocytes are associated with molecular and cellular markers of blood-brain barrier permeability in neonatal mice infected with the respiratory pathogen Bordetella pertussis.

Severe infection with the respiratory pathogen Bordetella pertussis during infancy has been associated with neurological complications, but the underlying mechanisms are not fully understood. Here we examined the impact of infection of neonatal mice with B. pertussis on the blood-brain barrier (BBB) by assessing pericytes, endothelial cells and tight junctions in cortex. We report that B. pertussis infection was associated with altered spatial distribution of brain pericytes, together with cerebral vasodilation and changes in endothelial cell tight junctions, as well as enhanced vascular deposition of the alarmin S100β. We demonstrate that, while there was an increase in the number of GFAP+ blood vessel-associated astrocytes, expression of the end foot marker, aquaporin 4 (AQP4), was decreased in these astrocytes. Microglia from the cortex of infected mice adopted a reactive morphology, migrated towards blood vessels and internalised AQP4 to a greater extent than microglia in un-infected mice. This study indicates that disruption of the BBB, inferred from structural and molecular alterations, during infection of neonatal mice with B. pertussis is linked to activation of vessel-associated microglia and astrocytes. Our findings suggest that the neurological sequelae associated with critical pertussis in infancy may be due, at least in part, to breakdown of the BBB.