Open AccessStaphylococcus aureus ‐mediated blood–brain barrier injury: an in vitro human brain microvascular endothelial cell model
Author(s) -
McLoughlin Alisha,
Rochfort Keith D.,
McDonnell Cormac J.,
Kerrigan Steven W.,
Cummins Philip M.
Publication year - 2017
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12664
Subject(s) - biology , proinflammatory cytokine , blood–brain barrier , staphylococcus aureus , chemokine , microbiology and biotechnology , multiplicity of infection , in vitro , tight junction , endothelium , immunology , context (archaeology) , inflammation , central nervous system , bacteria , neuroscience , biochemistry , paleontology , genetics , endocrinology
Summary Blood–brain barrier (BBB) disruption constitutes a hallmark event during pathogen‐mediated neurological disorders such as bacterial meningitis. As a prevalent opportunistic pathogen, Staphylococcus aureus (SA) is of particular interest in this context, although our fundamental understanding of how SA disrupts the BBB is very limited. This paper employs in vitro infection models to address this. Human brain microvascular endothelial cells (HBMvECs) were infected with formaldehyde‐fixed (multiplicity of infection [MOI] 0–250, 0–48 hr) and live (MOI 0–100, 0–3 hr) SA cultures. Both Fixed‐SA and Live‐SA could adhere to HBMvECs with equal efficacy and cause elevated paracellular permeability. In further studies employing Fixed‐SA, infection of HBMvECs caused dose‐dependent release of cytokines/chemokines (TNF‐α, IL‐6, MCP‐1, IP‐10, and thrombomodulin), reduced expression of interendothelial junction proteins (VE‐Cadherin, claudin‐5, and ZO‐1), and activation of both canonical and non‐canonical NF‐κB pathways. Using N‐acetylcysteine, we determined that these events were coupled to the SA‐mediated induction of reactive oxygen species (ROS) within HBMvECs. Finally, treatment of HBMvECs with Fixed‐ΔSpA (MOI 0–250, 48 hr), a gene deletion mutant of Staphylococcal protein A associated with bacterial infectivity, had relatively similar effects to Newman WT Fixed‐SA. In conclusion, these findings provide insight into how SA infection may activate proinflammatory mechanisms within the brain microvascular endothelium to elicit BBB failure.