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

iScience. 2022 Dec 19;26(1):105838. doi: 10.1016/j.isci.2022.105838. eCollection 2023 Jan 20.

Authors

Yvonne Adams¹, Anne Skovsbo Clausen², Peter Østrup Jensen^{3

4

5}, Malin Lager⁶, Peter Wilhelmsson^{6

7}, Anna J Henningson^{6

7}, Per-Eric Lindgren^{6

7}, Daniel Faurholt-Jepsen⁸, Helene Mens⁸, Peter Kraiczy⁹, Kasper Nørskov Kragh^{4

5}, Thomas Bjarnsholt^{4

5}, Andreas Kjaer², Anne-Mette Lebech^{8

10}, Anja R Jensen¹

Affiliations

¹ Centre for Medical Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Maersk Tower, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.
² Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
³ Department of Biomedical Sciences, University of Copenhagen, University Hospital-Rigshospitalet, Copenhagen, Denmark.
⁴ Department of Clinical Microbiology, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
⁵ Costerton Biofilm Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁶ National Reference Laboratory for Borrelia and Other Tick-Borne Bacteria, Division of Clinical Microbiology, Laboratory Medicine, Region Jönköping County and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
⁷ Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
⁸ Department of Infectious Diseases, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
⁹ Institute of Medical Microbiology and Infection Control, University Hospital of Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.
¹⁰ Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

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.

Keywords: Cell biology; Medical Microbiology; Neuroscience.