A possible role for inflammation in mediating apoptosis of oligodendrocytes as induced by the Lyme disease spirochete Borrelia burgdorferi

Abstract

BackgroundInflammation caused by the Lyme disease spirochete B. burgdorferi is an important factor in the pathogenesis of Lyme neuroborreliosis. Our central hypothesis is that B. burgdorferi can cause disease via the induction of inflammatory mediators such as cytokines and chemokines in glial and neuronal cells. Earlier we demonstrated that interaction of B. burgdorferi with brain parenchyma induces inflammatory mediators in glial cells as well as glial (oligodendrocyte) and neuronal apoptosis using ex vivo and in vivo models of experimentation.MethodsIn this study we evaluated the ability of live B. burgdorferi to elicit inflammation in vitro in differentiated human MO3.13 oligodendrocytes and in differentiated primary human oligodendrocytes, by measuring the concentration of immune mediators in culture supernatants using Multiplex ELISA assays. Concomitant apoptosis was quantified in these cultures by the in situ terminal deoxynucleotidyl transferase mediated UTP nick end labeling (TUNEL) assay and by quantifying active caspase-3 by flow cytometry. The above phenomena were also evaluated after 48 h of stimulation with B. burgdorferi in the presence and absence of various concentrations of the anti-inflammatory drug dexamethasone.ResultsB. burgdorferi induced enhanced levels of the cytokine IL-6 and the chemokines IL-8 and CCL2 in MO3.13 cells as compared to basal levels, and IL-8 and CCL2 in primary human oligodendrocytes, in a dose-dependent manner. These cultures also showed significantly elevated levels of apoptosis when compared with medium controls. Dexamethasone reduced both the levels of immune mediators and apoptosis, also in a manner that was dose dependent.ConclusionsThis finding supports our hypothesis that the inflammatory response elicited by the Lyme disease spirochete in glial cells contributes to neural cell damage. As oligodendrocytes are vital for the functioning and survival of neurons, the inflammation and subsequent apoptosis of oligodendrocytes induced by B. burgdorferi could contribute to the pathogenesis of Lyme neuroborreliosis.

Quetiapine mitigates the neuroinflammation and oligodendrocyte loss in the brain of C57BL/6 mouse following cuprizone exposure for one week

“…both the levels of IL-6 and apoptosis in a dose dependent manner (Ramesh et al, 2012). Similar to dexamethasone, QTP ameliorated both OLs loss and higher levels of IL-6 and TNF-α in the CPZ-exposed mice in the present study; in the meanwhile it improved the behavioral performance of the subjects.…”

The Lyme disease spirochete Borrelia burgdorferi induces inflammation and apoptosis in cells from dorsal root ganglia

“…The slides were then detached from the chamber and processed for immunofluorescence staining as previously described [25]. …”

Cytokine/Chemokine Responses in Activated CD4+and CD8+T Cells Isolated from Peripheral Blood, Bone Marrow, and Axillary Lymph Nodes during Acute Simian Immunodeficiency Virus Infection

“…All of the MAbs used in this assay are cross-reactive with RM cytokines/chemokines, as reported earlier (5,(30)(31)(32)(33)(34). The multiplex plate was read with a Bio-Plex 200 suspension array Luminex system (Bio-Rad) as reported previously (5,35).…”