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 Kjær, Anne‐Mette Lebech, Anja T. R. Jensen
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.