OspA-CD40 dyad: ligand-receptor interaction in the translocation of neuroinvasive Borrelia across the blood-brain barrier

Scientific Paper

Expression Proteomics, Gen. Pharma & Chemistry

10.1038/srep00086

MALDI-TOF

2011

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Lucia Pulzova1,2, Andrej Kovac2, Rastislav Mucha2, Patrik Mlynarcik1, Elena Bencurova1, Marian Madar2, Michal Novak2 & Mangesh Bhide1,2

1Laboratory of Biomedical Microbiology and Immunology, Department of Microbiology and Immunology, University of Veterinary Medicine and Pharmacy, 04181, Kosice, Slovakia, 2Institute of Neuroimmunology, Slovak Academy of Sciences, 84510 Bratislava, Slovakia.

nature SCIENTIFIC REPORTS | 1 : 86 | DOI: 10.1038/srep00086

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.

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