Borrelial adhesion to brain microvascular endothelial cells is mediated via OspA:CD40 dyad
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1
Slovak Academy of Sciences, Institute of Neuroimmunology, Slovakia
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2
University of veterinary medicine and farmacy, Department of microbiology, immunology and gnotobiology, Slovakia
Neuroborreliosis is the neurologic manifestation of Lyme disease, the most common tick-borne disease in northern hemisphere. Successful invasion of CNS is subjected to translocation of Borrelia across the blood-brain barrier (BBB). Borrelial traversal is a multi-stage process with unclear molecular principle. Main prerequisite for BBB traversal seems to be adhesion to endothelial cells (ECs).
To identify borrelial ligand interacting with EC receptor Ligand capture assay (LCA) coupled with MALDI-TOF-MS was employed. LCA showed that neuroinvasive Borrelia SKT-7.1 (B. bavariensis) possess a potential to interact with ECs. On the other hand, no EC interacting protein of non-neuroinvasive B. burgdorferi sensu stricto (SKT-2) was observed. Most abundant EC interacting SKT-7.1 protein was further identified as outer surface protein (OspA). To corroborate the OspA ligand interaction with EC receptors, His-tagged OspA proteins of both strains were constructed and hybridized with whole cell lysate of ECs in ALBI assay and co-precipitation. Co-precipitant of SKT-7.1 His-tagged OspA of was identified as CD40. No co-precipitant was detected in experiment with SKT-2 OspA.
Taken together, study indicates that OspA is important molecule in the adhesion to ECs and provides Borrelia with an essential function in adhesion and neuroinvasion. It can be concluded that initial adhesion are mediated via OspA:CD40 dyad. Moreover, different binding ability of OspA SKT-7.1 and SKT-2 to CD40 may play a role in diverse borrelial residence in host tissues.
Acknowledgements
Work/infrastructure were supported by grants: APVV-0036-10, VEGA 1/0054/12, EU structural funds-26220120002 (INFEKTZOON). His-tagged OspAs were kind gift provided by E. Chakurkar, ICAR, Goa India.
Keywords:
host:pathogen interactions,
Borrelia burgdorferi Group,
Central Nervous System,
Proteomics,
Blood-Brain Barrier
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Host-pathogen interactions
Citation:
Pulzova
L,
Kovac
A,
Bencurova
E,
Mucha
R,
Cepkova
M and
Bhide
M
(2013). Borrelial adhesion to brain microvascular endothelial cells is mediated via OspA:CD40 dyad.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.01181
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Received:
15 Jul 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Lucia Pulzova, Slovak Academy of Sciences, Institute of Neuroimmunology, Bratislava, 842 45, Slovakia, pulzova.lucia@gmail.com