title: The Lyme disease spirochete Borrelia burgdorferi induces inflammation and apoptosis in cells from dorsal root ganglia.
abstract: BACKGROUND
  Lyme neuroborreliosis (LNB), caused by the spirochete Borrelia burgdorferi, affects both the peripheral and the central nervous systems. Radiculitis or nerve root inflammation, which can cause pain, sensory loss, and weakness, is the most common manifestation of peripheral LNB in humans. We previously reported that rhesus monkeys infected with B. burgdorferi develop radiculitis as well as inflammation in the dorsal root ganglia (DRG), with elevated levels of neuronal and satellite glial cell apoptosis in the DRG. We hypothesized that B. burgdorferi induces inflammatory mediators in glial and neuronal cells and that this inflammatory milieu precipitates glial and neuronal apoptosis.
  
  
  METHODS
  To model peripheral neuropathy in LNB we incubated normal rhesus DRG tissue explants with live B. burgdorferi ex vivo and identified immune mediators, producer cells, and verified the presence of B. burgdorferi in tissue sections by immunofluorescence staining and confocal microscopy. We also set up primary cultures of DRG cells from normal adult rhesus macaques and incubated the cultures with live B. burgdorferi. Culture supernatants were subjected to multiplex ELISA to detect immune mediators, while the cells were evaluated for apoptosis by the in situ TUNEL assay. A role for inflammation in mediating apoptosis was assessed by evaluating the above phenomena in the presence and absence of various concentrations of the anti-inflammatory drug dexamethasone. As Schwann cells ensheath the dorsal roots of the DRG, we evaluated the potential of live B. burgdorferi to induce inflammatory mediators in human Schwann cell (HSC) cultures.
  
  
  RESULTS
  Rhesus DRG tissue explants exposed to live B. burgdorferi showed localization of CCL2 and IL-6 in sensory neurons, satellite glial cells and Schwann cells while IL-8 was seen in satellite glial cells and Schwann cells. Live B. burgdorferi induced elevated levels of IL-6, IL-8 and CCL2 in HSC and DRG cultures and apoptosis of sensory neurons. Dexamethasone reduced the levels of immune mediators and neuronal apoptosis in a dose dependent manner.
  
  
  CONCLUSIONS
  In this model, B. burgdorferi induced an inflammatory response and neuronal apoptosis of DRG. These pathophysiological processes could contribute to peripheral neuropathy in LNB.
authors.affiliation: Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Covington, LA, USA.
authors.forename: Geeta
authors.initials: G
authors.lastname: Ramesh
authors.forename: Lenay
authors.initials: L
authors.lastname: Santana-Gould
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Inglis
authors.forename: John D
authors.initials: JD
authors.lastname: England
authors.forename: Mario T
authors.initials: MT
authors.lastname: Philipp
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D025065:Borrelia burgdorferi; D018932:Chemokine CCL2 / Q000096:biosynthesis; D003470:Culture Media / Q000737:chemistry; D003593:Cytoplasm / Q000473:pathology; D003907:Dexamethasone / Q000627:therapeutic use; D005455:Fluorescent Antibody Technique; D005727:Ganglia, Spinal / Q000473:pathology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000209:etiology / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008193:Lyme Disease / Q000150:complications / Q000473:pathology*; D008253:Macaca mulatta; D018613:Microscopy, Confocal; D009474:Neurons / Q000473:pathology; D027161:Satellite Cells, Perineuronal / Q000473:pathology; D012583:Schwann Cells / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2; D003470:Culture Media; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D003907:Dexamethasone