A journey into the brain: insight into how bacterial pathogens cross blood–brain barriers

• Published in: Nature reviews. Microbiology 2017-03, Vol.15 (3), p.149-159
• Main Authors: Coureuil, Mathieu, Lécuyer, Hervé, Bourdoulous, Sandrine, Nassif, Xavier
• Format: Article
• Language: English
• Subjects: 631/326/107; 631/326/41/1969/1317; 631/326/41/2531; 692/699/255/1638; Bacteria; Bacterial infections; Bacteriology; Blood-brain barrier; Blood-Brain Barrier - microbiology; Brain; Drug Delivery Systems; E coli; Escherichia coli; Escherichia coli - pathogenicity; Human health and pathology; Humans; Infectious Diseases; Life Sciences; Medical Microbiology; Membranes; Meninges - microbiology; Meningitis; Meningitis, Bacterial - microbiology; Meningitis, Bacterial - pathology; Microbiology; Microbiology and Parasitology; Neisseria meningitidis; Neisseria meningitidis - pathogenicity; Nervous system; Parasitology; Pathogenic microorganisms; Pathogens; Physiological aspects; review-article; Risk factors; Spinal cord; Streptococcus; Streptococcus agalactiae - pathogenicity; Streptococcus infections; Streptococcus pneumoniae; Streptococcus pneumoniae - pathogenicity; Virology
• ISSN: 1740-1526; 1740-1534
• DOI: 10.1038/nrmicro.2016.178

Key Points The blood–central nervous system (CNS) barriers are tight and protect the brain parenchyma from insults, including those of infectious origin. This barrier function is due to the presence of tight junctions between the endothelial cells of the brain. The formation of these junctions is the consequence of interactions inside the neurovascular unit. There are two blood–CNS barriers that can potentially be circumvented by bacterial pathogens: the blood–brain barrier (BBB) and the blood–cerebrospinal fluid barrier (BCSFB). The BCSFB corresponds to the choroid plexuses and the microvessels of the leptomeninges. Bacteria can invade the meninges from the bloodstream through the choroid plexuses or directly through the microvessels of the leptomeninges and/or the brain parenchyma. In the case of crossing from parenchyma vessels, bacteria are drained to the subarachnoid space through the glymphatic pathway. Regardless of the site of crossing, meningeal invasion requires the crossing of two cellular barriers: an endothelial monolayer (in the choroid plexus or in the brain parenchyma and/or leptomeninges) followed by an epithelial monolayer (the choroid plexus ependyma, or the leptomeningeal monolayer of the pia mater or of a subarachnoid trabecula). A limited number of blood-borne bacteria can cross the blood–CNS barriers and cause meningitis. The extracellular pathogens that are involved are usually Neisseria meningitidis , Streptococcus pneumoniae or, in newborns, group B Streptococcus and Escherichia coli K1. Regardless of the mechanisms that are used to invade the meninges from the bloodstream, the level of bacteraemia plays a key part in meningeal tropism. The extracellular bacteria interact directly with the blood–CNS barriers. N. meningitidis is believed to cross the blood–CNS barriers by interacting with the leptomeninges and/or brain microvessels, and to open intercellular junctions following signals that are induced by the adhesion of bacteria to the endothelial cells. S. pneumoniae invades the meninges following interaction with the brain microvessels and is believed to transcytose through the endothelial cells following interactions with several host cell receptors. E. coli is believed to transcytose through endothelial cells, to have several attributes that enable it to adhere to endothelial cells and to induce signalling events that lead to bacterial invasion. Bacteria have to overcome many obstacles to invade the meninges from the bloodstre