3D blood-brain barrier-organoids as a model for Lyme neuroborreliosis highlighting genospecies dependent organotropism
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Lyme neuroborreliosis (LNB), a tick-borne infection caused by spirochetes within the Borrelia burgdorferi sensu lato (s.L.) complex, is among the most prevalent bacterial central nervous system (CNS) infections in Europe and the US. Here we have screened a panel of low-passage B. burgdorferi s.l. isolates using a novel, human-derived 3D blood-brain barrier (BBB)-organoid model. We show that human-derived BBB-organoids support the entry of Borrelia spirochetes, leading to swelling of the organoids and a loss of their structural integrity. The use of the BBB-organoid model highlights the organotropism between B. burgdorferi s.l. genospecies and their ability to cross the BBB contributing to CNS infection.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 105838 |
| Tidsskrift | iScience |
| Vol/bind | 26 |
| Udgave nummer | 1 |
| ISSN | 2589-0042 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
We thank Mette Ulla Madsen and the Core Facility for Integrated Microscopy, Faculty of Health and Medical Sciences, University of Copenhagen for excellent technical assistance. We also thank Professor Sven Bergström, Umeå University, Sweden, for kindly providing the clinical isolates of B. burgdorferi s.l. and Professor Jon Skare, Texas A&M University, USA for providing the plasmid pBBE22luc. The research performed at the Centre for Medical Parasitology, University of Copenhagen was supported by grants from the Danish Ministry of Food, Agriculture and Fisheries (3R-Center Research Grant), and the Lundbeck Foundation ( R180-2014-3098 , R313-2019-322 and R324-2019-2029 ). The research performed at the Department of Infectious Diseases, University Hospital, Rigshospitalet was supported by a grant from the Lundbeck Foundation ( R366-2021-127 ). This study was partially supported by a grant of the European Union through the European Regional Development Fund and the Interreg NorthSea Region Program 2014–2020 as part of the NorthTick project (reference number J-No: 38-2-7-19).
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© 2022
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