Defense at the Border: The Blood–Brain Barrier Versus Bacterial Foreigners

Abstract

Bacterial meningitis is among the top ten causes of infectious disease-related deaths worldwide, with up to half of the survivors left with permanent neurological sequelae. The blood–brain barrier (BBB), composed mainly of specialized brain microvascular endothelial cells, maintains biochemical homeostasis in the CNS by regulating the passage of nutrients, molecules and cells from the blood to the brain. Despite its highly restrictive nature, certain bacterial pathogens are able to gain entry into the CNS resulting in serious disease. In recent years, important advances have been made in understanding the molecular and cellular events that are involved in the development of bacterial meningitis. In this review, we summarize the progress made in elucidating the molecular mechanisms of bacterial BBB-crossing, highlighting common themes of host–pathogen interaction, and the potential role of the BBB in innate defense during infection.

Keywords:

• blood–brain barrier
• Escherichia coli K1
• group B Streptococcus
• Haemophilus influenzae type B
• meningitis
• Neisseria meningitidis
• neutrophil
• Streptococcus pneumoniae
• tight/adherens junction

Acknowledgements

The authors appreciate the contribution of the anonymous peer reviewers and apologize to researchers whose work has not been discussed in detail or reviewed here due to space constraints.

Financial & competing interests disclosure

Work on the blood–brain barrier and bacterial meningitis in KS Doran‘s laboratory is supported by funding from the NIH/NINDS (grant no. RO1NS051247). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Work on the blood–brain barrier and bacterial meningitis in KS Doran‘s laboratory is supported by funding from the NIH/NINDS (grant no. RO1NS051247). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.