title: The multifaceted responses of primary human astrocytes and brain microvascular endothelial cells to the Lyme disease spirochete, Borrelia burgdorferi.
abstract: The vector-borne pathogen, Borrelia burgdorferi, causes a multi-system disorder including neurological complications. These neurological disorders, collectively termed neuroborreliosis, can occur in up to 15% of untreated patients. The neurological symptoms are probably a result of a glial-driven, host inflammatory response to the bacterium. However, the specific contributions of individual glial and other support cell types to the pathogenesis of neuroborreliosis are relatively unexplored. The goal of this project was to characterize specific astrocyte and endothelial cell responses to B. burgdorferi. Primary human astrocytes and primary HBMEC (human brain microvascular endothelial cells) were incubated with B. burgdorferi over a 72-h period and the transcriptional responses to the bacterium were analyzed by real-time PCR arrays. There was a robust increase in several surveyed chemokine and related genes, including IL (interleukin)-8, for both primary astrocytes and HBMEC. Array results were confirmed with individual sets of PCR primers. The production of specific chemokines by both astrocytes and HBMEC in response to B. burgdorferi, including IL-8, CXCL-1, and CXCL-10, were confirmed by ELISA. These results demonstrate that primary astrocytes and HBMEC respond to virulent B. burgdorferi by producing a number of chemokines. These data suggest that infiltrating phagocytic cells, particularly neutrophils, attracted by chemokines expressed at the BBB (blood-brain barrier) may be important contributors to the early inflammatory events associated with neuroborreliosis.
authors.affiliation: Microbiology and Immunology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58203, USA. catherine.brissette@med.und.edu
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Brissette
authors.forename: Eric D
authors.initials: ED
authors.lastname: Kees
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Burke
authors.forename: Robert A
authors.initials: RA
authors.lastname: Gaultney
authors.forename: Angela M
authors.initials: AM
authors.lastname: Floden
authors.forename: John A
authors.initials: JA
authors.lastname: Watt
mesh_terms: D001253:Astrocytes / Q000473:pathology*; D001812:Blood-Brain Barrier / Q000502:physiology; D025065:Borrelia burgdorferi; D002196:Capillaries / Q000473:pathology*; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D018076:DNA, Complementary / Q000096:biosynthesis; D042783:Endothelial Cells / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000502:physiology; D020869:Gene Expression Profiling; D006801:Humans; D007962:Leukocytes / Q000502:physiology; D020852:Lyme Neuroborreliosis / Q000382:microbiology* / Q000473:pathology*; D046228:Microarray Analysis; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D016133:Polymerase Chain Reaction; D061251:Primary Cell Culture; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D015854:Up-Regulation / Q000502:physiology
chemical_list: D018925:Chemokines; D016207:Cytokines; D018076:DNA, Complementary; D009419:Nerve Tissue Proteins; D012313:RNA