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

Scientific Reports
Lucia PulzovaMangesh Bhide

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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Citations

Sep 28, 2014·Microbiological Research·Patrik MlynarcikMangesh R Bhide
Jan 23, 2015·Tissue Barriers·Rebecca L McCallRachael W Sirianni
May 21, 2016·Parasite Immunology·J de la FuenteC Maritz-Olivier
May 27, 2016·Molecular BioSystems·Anita HorvatićMangesh Bhide
Aug 2, 2018·Expert Review of Proteomics·Sara Artigas-JerónimoMargarita Villar
Oct 16, 2018·Frontiers in Microbiology·Evelína KánováMangesh Bhide
Jan 29, 2013·Médecine sciences : M/S·Burcu Kaplan-Türköz, Laurent Terradot
Oct 4, 2020·Neurochemistry International·Maryam VasefiAnthony Osu
Jul 3, 2021·Brain Sciences·Lenzie Ford, Danielle M Tufts

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Datasets Mentioned

BETA
GU906888
GU320003

Methods Mentioned

BETA
PCR
ligand capture assay
co-immunoprecipitation
Co-IP
Assay
X-ray
PCRs

Software Mentioned

IQ5
SMART
flexAnalysis
Geneious
Mascot

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