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
Affiliations
Yvonne Adams
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; Corresponding author
Anne Skovsbo Clausen
Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark
Peter Østrup Jensen
Department of Biomedical Sciences, University of Copenhagen, University Hospital-Rigshospitalet, Copenhagen, Denmark; Department of Clinical Microbiology, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark; Costerton Biofilm Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Malin Lager
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
Peter Wilhelmsson
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; Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
Anna J. Henningson
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; Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
Per-Eric Lindgren
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; Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
Daniel Faurholt-Jepsen
Department of Infectious Diseases, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark
Helene Mens
Department of Infectious Diseases, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark
Peter Kraiczy
Institute of Medical Microbiology and Infection Control, University Hospital of Frankfurt, Goethe University Frankfurt, Frankfurt, Germany
Kasper Nørskov Kragh
Department of Clinical Microbiology, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark; Costerton Biofilm Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Thomas Bjarnsholt
Department of Clinical Microbiology, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark; Costerton Biofilm Center, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Andreas Kjaer
Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark
Anne-Mette Lebech
Department of Infectious Diseases, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
Anja R. Jensen
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; Corresponding author
Summary: 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.
