Abstract
Abstract Infection is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Curli is a bacterial amyloid that serves as a component of enteric bacterial biofilms. Patients are exposed to curli during urinary tract infections, gastrointestinal infections, and sepsis. Here we studied the immune response to curli amyloids in the context of murine SLE. We found that curli amyloids from bacterial cultures contain abundant nucleic acids and that exogenous DNA enhances amyloid fibrillization. Bone marrow-derived myeloid DCs strongly respond to curli-DNA composites, producing large quantities of IL-12, IL-6, and IL-10. Curli potently induces expression of IFN-β and IFN-stimulated genes. Using both natural and synthetic curli, we found that curli and nucleic acids synergize to activate DCs. Young, pre-disease lupus-prone NZBW-F1 mice injected i.p. with nucleic acid-containing curli produce high titers of anti-dsDNA and anti-chromatin autoantibodies within 2 weeks of the first injection, much earlier than mice treated with PBS. In conclusion, the bacterial amyloid curli contains nucleic acids which are integral to the immune response to bacterial biofilms. Curli is a potent activator of dendritic cells and can rapidly accelerate autoimmunity in lupus-prone mice. This work suggests that nucleic acid-containing bacterial amyloids are an important environmental trigger for lupus and that curli injection may be a novel method to accelerate murine lupus.
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