3D blood-brain barrier-organoids as a model for Lyme neuroborreliosis highlighting genospecies dependent organotropism

Yvonne Adams; Anne Skovsbo Clausen; Peter Østrup Jensen; Malin Lager; Peter Wilhelmsson; Anna J Henningson; Per-Eric Lindgren; Daniel Faurholt-Jepsen; Helene Mens; Peter Kraiczy; Kasper Nørskov Kragh; Thomas Bjarnsholt; Andreas Kjaer; Anne-Mette Lebech; Anja R Jensen

doi:10.1016/j.isci.2022.105838

3D blood-brain barrier-organoids as a model for Lyme neuroborreliosis highlighting genospecies dependent organotropism

Yvonne Adams^*, Anne Skovsbo Clausen, Peter Østrup Jensen, Malin Lager, Peter Wilhelmsson, Anna J Henningson, Per-Eric Lindgren, Daniel Faurholt-Jepsen, Helene Mens, Peter Kraiczy, Kasper Nørskov Kragh, Thomas Bjarnsholt, Andreas Kjaer, Anne-Mette Lebech, Anja R Jensen^*

^*Corresponding author af dette arbejde

Abstrakt

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
Sider (fra-til)	105838
ISSN	2589-0042
DOI	https://doi.org/10.1016/j.isci.2022.105838
Status	Udgivet - 20 jan. 2023

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10.1016/j.isci.2022.105838

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Adams, Y., Clausen, A. S., Jensen, P. Ø., Lager, M., Wilhelmsson, P., Henningson, A. J., Lindgren, P-E., Faurholt-Jepsen, D., Mens, H., Kraiczy, P., Kragh, K. N., Bjarnsholt, T., Kjaer, A., Lebech, A-M., & Jensen, A. R. (2023). 3D blood-brain barrier-organoids as a model for Lyme neuroborreliosis highlighting genospecies dependent organotropism. iScience, 26(1), 105838. [105838]. https://doi.org/10.1016/j.isci.2022.105838

Adams, Y, Clausen, AS, Jensen, PØ, Lager, M, Wilhelmsson, P, Henningson, AJ, Lindgren, P-E, Faurholt-Jepsen, D , Mens, H, Kraiczy, P, Kragh, KN , Bjarnsholt, T , Kjaer, A , Lebech, A-M & Jensen, AR 2023, '3D blood-brain barrier-organoids as a model for Lyme neuroborreliosis highlighting genospecies dependent organotropism', iScience, bind 26, nr. 1, 105838, s. 105838. https://doi.org/10.1016/j.isci.2022.105838

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title = "3D blood-brain barrier-organoids as a model for Lyme neuroborreliosis highlighting genospecies dependent organotropism",

abstract = "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.",

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AU - Lager, Malin

AU - Wilhelmsson, Peter

AU - Henningson, Anna J

AU - Lindgren, Per-Eric

AU - Faurholt-Jepsen, Daniel

AU - Mens, Helene

AU - Kraiczy, Peter

AU - Kragh, Kasper Nørskov

AU - Bjarnsholt, Thomas

AU - Kjaer, Andreas

AU - Lebech, Anne-Mette

AU - Jensen, Anja R

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AB - 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.

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3D blood-brain barrier-organoids as a model for Lyme neuroborreliosis highlighting genospecies dependent organotropism

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