title: OspA-CD40 dyad: ligand-receptor interaction in the translocation of neuroinvasive Borrelia across the blood-brain barrier.
abstract: Lyme borreliosis is the most widespread vector-borne disease in temperate zones of Europe and North America. Although the infection is treatable, the symptoms are often overlooked resulting in infection of the neuronal system. In this work we uncover the underlying molecular mechanism of borrelial translocation across the blood-brain barrier (BBB). We demonstrate that neuroinvasive strain of Borrelia readily crosses monolayer of brain-microvascular endothelial cells (BMECs) in vitro and BBB in vivo. Using protein-protein interaction assays we found that CD40 of BMECs and OspA of Borrelia are the primary molecules in transient tethering of Borrelia to endothelium. OspA of neuroinvasive Borrelia, but not of non-neuroinvasive strain, binds CD40. Furthermore, only the neuroinvasive Borrelia and its recombinant OspA activated CD40-dependent pathway in BMECs and induced expression of integrins essential for stationary adhesion. Demonstration of the CD40-ligand interactions may provide a new possible perspective on molecular mechanisms of borrelial BBB translocation process.
authors.affiliation: Laboratory of Biomedical Microbiology and Immunology, Department of Microbiology and Immunology, University of Veterinary Medicine and Pharmacy, 04181, Kosice, Slovakia.
authors.forename: Lucia
authors.initials: L
authors.lastname: Pulzova
authors.forename: Andrej
authors.initials: A
authors.lastname: Kovac
authors.forename: Rastislav
authors.initials: R
authors.lastname: Mucha
authors.forename: Patrik
authors.initials: P
authors.lastname: Mlynarcik
authors.forename: Elena
authors.initials: E
authors.lastname: Bencurova
authors.forename: Marian
authors.initials: M
authors.lastname: Madar
authors.forename: Michal
authors.initials: M
authors.lastname: Novak
authors.forename: Mangesh
authors.initials: M
authors.lastname: Bhide
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D001428:Bacterial Vaccines / Q000378:metabolism*; D001483:Base Sequence; D001692:Biological Transport; D001812:Blood-Brain Barrier; D025065:Borrelia burgdorferi / Q000472:pathogenicity*; D001921:Brain / Q000382:microbiology*; D019013:CD40 Antigens / Q000378:metabolism*; D017931:DNA Primers; D008024:Ligands; D008074:Lipoproteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D019013:CD40 Antigens; D017931:DNA Primers; D008024:Ligands; D008074:Lipoproteins; C072045:OspA protein; D011956:Receptors, Cell Surface