Mechanisms of Blood Brain Barrier Disruption by Different Types of Bacteria, and Bacterial–Host Interactions Facilitate the Bacterial Pathogen Invading the Brain

Abstract

This review aims to elucidate the different mechanisms of blood brain barrier (BBB) disruption that may occur due to invasion by different types of bacteria, as well as to show the bacteria-host interactions that assist the bacterial pathogen in invading the brain. For example, platelet-activating factor receptor (PAFR) is responsible for brain invasion during the adhesion of pneumococci to brain endothelial cells, which might lead to brain invasion. Additionally, the major adhesin of the pneumococcal pilus-1, RrgA is able to bind the BBB endothelial receptors: polymeric immunoglobulin receptor (pIgR) and platelet endothelial cell adhesion molecule (PECAM-1), thus leading to invasion of the brain. Moreover, Streptococcus pneumoniae choline binding protein A (CbpA) targets the common carboxy-terminal domain of the laminin receptor (LR) establishing initial contact with brain endothelium that might result in BBB invasion. Furthermore, BBB disruption may occur by S. pneumoniae penetration through increasing in pro-inflammatory markers and endothelial permeability. In contrast, adhesion, invasion, and translocation through or between endothelial cells can be done by S. pneumoniae without any disruption to the vascular endothelium, upon BBB penetration. Internalins (InlA and InlB) of Listeria monocytogenes interact with its cellular receptors E-cadherin and mesenchymal-epithelial transition (MET) to facilitate invading the brain. L. monocytogenes species activate NF-κB in endothelial cells, encouraging the expression of P- and E-selectin, intercellular adhesion molecule 1 (ICAM-1), and Vascular cell adhesion protein 1 (VCAM-1), as well as IL-6 and IL-8 and monocyte chemoattractant protein-1 (MCP-1), all these markers assist in BBB disruption. Bacillus anthracis species interrupt both adherens junctions (AJs) and tight junctions (TJs), leading to BBB disruption. Brain microvascular endothelial cells (BMECs) permeability and BBB disruption are induced via interendothelial junction proteins reduction as well as up-regulation of IL-1α, IL-1β, IL-6, TNF-α, MCP-1, macrophage inflammatory proteins-1 alpha (MIP1α) markers in Staphylococcus aureus species. Streptococcus agalactiae or Group B Streptococcus toxins (GBS) enhance IL-8 and ICAM-1 as well as nitric oxide (NO) production from endothelial cells via the expression of inducible nitric oxide synthase (iNOS) enhancement, resulting in BBB disruption. While Gram-negative bacteria, Haemophilus influenza OmpP2 is able to target the common carboxy-terminal domain of LR to start initial interaction with brain endothelium, then invade the brain. H. influenza type b (HiB), can induce BBB permeability through TJ disruption. LR and PAFR binding sites have been recognized as common routes of CNS entrance by Neisseria meningitidis. N. meningitidis species also initiate binding to BMECs and induces AJs deformation, as well as inducing specific cleavage of the TJ component occludin through the release of host MMP-8. Escherichia coli bind to BMECs through LR, resulting in IL-6 and IL-8 ...

Meningitic Escherichia coli Induction of ANGPTL4 in Brain Microvascular Endothelial Cells Contributes to Blood–Brain Barrier Disruption via ARHGAP5/RhoA/MYL5 Signaling Cascade

“…The alteration of intercellular tight junction is widely recognized as an important hallmark in meningitic bacterial induction of the BBB disruption, which could be mediated by a direct regulation of the tight junction proteins, as well as by an indirect inflammatory response-mediated tight junction damage [35][36][37][38][39]. However, interestingly, we demonstrated in this work that meningitic E. coli-caused ANGPTL4 induction of BBB disruption depended neither on direct damage of the tight junction proteins by ANGPTL4, nor the ANGPTL4-mediated proinflammatory cytokines production-by the demonstrations that all canonical tight junction proteins like ZO-1, Claudin 5, Occludin; the proinflammatory cytokines involving in BBB disruption like IFN-γ, IL-1β, TNF-α, IL-6, IL-8 [35,39]; as well as the potential endothelial activation markers like EGR-1, E-selectin, ICAM-1, and VEGFA were actually not affected in response to ANGPTL4 treatment or overexpression, which suggested that there might be a novel mechanism of ANGPTL4-mediated BBB disruption during meningitic E. coli infection process. Thus, here comes the question of how ANGPTL4 affects the barrier function of cells.…”

The Role of Periodontitis and Periodontal Bacteria in the Onset and Progression of Alzheimer’s Disease: A Systematic Review

“…There is evidence showing that these molecules reach or influence the CNS via the systemic circulation or neuronal paths. To reach the CNS, inflammatory cytokines have to cross the hematoencephalic barrier, which they can achieve in different ways such as modifying its permeability [58], binding to hematoencephalic barrier-free areas like circumentricular organs, passing through fenestrated capillaries, or using specific carriers [59].…”

“…Alzheimer's disease pathogenesis involves different bacterial species, like Chlamydia pneumoniae, Helicobacter pylori, and spirochetes [58,65]. These bacteria have been found in different anatomical sections of the CNS, but their primary etiological role in the onset of Alzheimer's disease is still being discussed, even if more evidence about their ability to invade the CNS and interfere with the basic mechanisms of the disease are coming to light.…”

circ_2858 Helps Blood-Brain Barrier Disruption by Increasing VEGFA via Sponging miR-93-5p during Escherichia coli Meningitis

“… 5 Accumulating evidence has suggested that meningitic pathogens enhance BBB permeability by degrading TJ proteins and that infection-induced neuroinflammatory responses largely aggravate CNS dysfunction. 6 , 7 Meanwhile, several host factors, such as transforming growth factor β1 (TGF-β1), matrix metallopeptidases (MMPs), and vascular endothelial growth factor A (VEGFA) are involved in the regulation of BBB permeability. 8 , 9 , 10 The identification of the key molecules involved in BBB disruption induced by different CNS-infecting bacteria is of great significance; however, the underlying mechanisms by which these key factors regulate BBB permeability in response to infection remain largely unclear.…”