Borrelia burgdorferi pathogenic potential correlates with type I and type III IFN production by human immune cells. (56.18)

Abstract

Borrelia burgdorferi (Bb) is the extracellular bacterial agent of Lyme disease. Bb elicits type I interferon (IFN) in humans via Toll-like receptors 7 and 9. Bb clinical isolates with different pathogenic potential were tested for their ability to induce IFNs in human peripheral blood mononuclear cells (PBMCs). Disseminating Bb isolates induced significantly higher levels of both type I (IFN-α) and type III IFN (IFN-λ) than did non-disseminating Bb isolates. In contrast, there was no significant difference in type II IFN (IFN-γ) production, nor in levels of IL-2, 6, 8, 10. However, non-disseminating Bb isolates induced significantly higher levels of TNF-α and IL-1β. In addition, disseminating clinical isolates were able to directly induce multiple IFN-responsive genes; non-disseminating strains required IFN-feedback signaling. A mutant of Bb was identified that was unable to induce a robust IFN-α response when compared to wild-type (wt); IFN-γ levels were not affected. Wt and mutant Bb were GFP-tagged and assessed for their ability to be phagocytosed by human immune cell populations using flow cytometry and fluorescence microscopy. There were more wt than mutant Bb associated with (p=0.01) and internalized by (p=0.034) PBMCs. These findings suggest that disseminating and non-disseminating clinical isolates may be differentially phagocytosed by dendritic cells. Intriguingly, the differential uptake appears to be mediated by factor(s) encoded on a single linear plasmid of Bb.