Bacterial amyloids from biofilms induce type I interferon response in plasmacytoid dendritic cells

Abstract

Abstract An increased expression of type I interferon (IFN) regulated genes is a hallmark of systemic lupus erythematosus, a complex autoimmune inflammatory disease. Although the exact etiology of lupus is unknown, infections can be an important environmental trigger for flares, and are a major cause of morbidity and mortality. Medically, bacterial biofilms are important for the establishment of chronic, persistent infections. Bacteria within these aggregates are embedded into their biofilms, allowing them to dramatically increase their ability to withstand physical insults and tolerate host defenses. To strengthen the extracellular matrix of their biofilms, bacteria produce amyloids, complex proteins with a conserved beta sheet structure. We have reported that Salmonella and E. coli biofilms contain the functional amyloid protein curli, which complexes with eukaryotic and bacterial DNA. Systemic administration of curli-DNA complexes accelerated autoimmunity in lupus-prone mice. Infections with curli-expressing Salmonella or E. coli gave the same results, implicating curli as a pathogenic factor in how biofilm-producing infections may contribute to lupus pathogenesis. We present here for the first time that bacterial amyloid curli activates plasmacytoid dendritic cells (pDCs), the primary producer of type I IFNs, in vitro. Additionally, we show that curli induces a robust production of IFNα and expression of interferon-stimulated genes, including CXCL10. Furthermore, curli induces in vivo activation of DCs in lupus-prone and wild-type mice. Our results identify bacterial amyloid curli as a novel activator of pDCs, and suggest that curli may accelerate lupus by directly activating pDCs and their powerful type I IFN activity.