The Lyme disease bacterium, Borrelia burgdorferi, stimulates an inflammatory response in human choroid plexus epithelial cells

• Published in: PloS one 2020-07, Vol.15 (7), p.e0234993-e0234993
• Main Authors: Thompson, Derick, Sorenson, Jordyn, Greenmyer, Jacob, Brissette, Catherine A, Watt, John A
• Format: Article
• Language: English
• Subjects: Adherens junctions; Animal models; Antibodies; Apoptosis; Bacteria; Bacterial infections; Biological activity; Biology and Life Sciences; Blood; Blood-Brain Barrier; Borrelia burgdorferi; Borrelia burgdorferi - immunology; Borrelia burgdorferi - pathogenicity; Cell adhesion & migration; Cell culture; Cell junctions; Cells, Cultured; Central nervous system; Central nervous system diseases; Cerebrospinal fluid; Chemokines; Chemotaxis; Choroid plexus; Choroid Plexus - immunology; Choroid Plexus - microbiology; Choroid Plexus - pathology; Complications; Complications and side effects; Cytokines; Development and progression; Epithelial cells; Epithelial Cells - immunology; Epithelial Cells - microbiology; Epithelial Cells - pathology; Gene Expression; Gene Expression Profiling; Gene sequencing; Genes; Health aspects; Humans; Immune response; Immune system; Immunomodulation; Infections; Inflammation; Inflammation - metabolism; Inflammatory response; Interferon; Lyme disease; Lyme Disease - immunology; Lyme Disease - microbiology; Lyme Disease - pathology; Medicine and Health Sciences; Meningitis; Neurological complications; Nutrients; Parenchyma; Pathogenesis; Physiological aspects; Proteins; Proteins - analysis; Ribonucleic acid; Risk factors; RNA; RNA - analysis; Signs and symptoms; Vector-borne diseases
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0234993

The main functions of the choroid plexus (CP) are the production of cerebral spinal fluid (CSF), the formation of the blood-CSF barrier, and regulation of immune response. This barrier allows for the exchange of specific nutrients, waste, and peripheral immune cells between the blood stream and CSF. Borrelia burgdorferi (Bb), the causative bacteria of Lyme disease, is associated with neurological complications including meningitis-indeed, Bb has been isolated from the CSF of patients. While it is accepted that B. burgdorferi can enter the central nervous system (CNS) of patients, it is unknown how the bacteria crosses this barrier and how the pathogenesis of the disease leads to the observed symptoms in patients. We hypothesize that during infection Borrelia burgdorferi will induce an immune response conducive to the chemotaxis of immune cells and subsequently lead to a pro-inflammatory state with the CNS parenchyma. Primary human choroid plexus epithelial cells were grown in culture and infected with B. burgdorferi strain B31 MI-16 for 48 hours. RNA was isolated and used for RNA sequencing and RT-qPCR validation. Secreted proteins in the supernatant were analyzed via ELISA. Transcriptome analysis based on RNA sequencing determined a total of 160 upregulated genes and 98 downregulated genes. Pathway and biological process analysis determined a significant upregulation in immune and inflammatory genes specifically in chemokine and interferon related pathways. Further analysis revealed downregulation in genes related to cell to cell junctions including tight and adherens junctions. These results were validated via RT-qPCR. Protein analysis of secreted factors showed an increase in inflammatory chemokines, corresponding to our transcriptome analysis. These data further demonstrate the role of the CP in the modulation of the immune response in a disease state and give insight into the mechanisms by which Borrelia burgdorferi may disseminate into, and act upon, the CNS. Future experiments aim to detail the impact of B. burgdorferi on the blood-CSF-barrier (BCSFB) integrity and inflammatory response within animal models.