Bacterial biofilms are bacterial communities, abundant in the human microbiome and in chronic infections. We have previously found that bacterial and eukaryotic DNA are incorporated into curli fibers, functional bacterial amyloids present in biofilms. Curli/DNA complexes activate conventional dendritic cells to produce pro-inflammatory cytokines and Type I-Interferons. Curli/DNA complexes accelerated autoantibodies production in lupus-prone NZBxW/F1 mice and also in wild type mice, suggesting curli/DNA complexes can break tolerance in lupus. We proposed to study how curli affect major pathogenic steps in lupus and discovered that 1) bacterial amyloid curli acts as a carrier for DNA to elicit autoimmunity via TLR2 and TLR9. 2) curli/DNA complexes directly stimulate Plasmacytoid Dendritic cells (pDCs) to produce type I Interferons. 3) Bacterial amyloids directly stimulate B cells to break tolerance in lupus. Indeed, curli/DNA complexes induce B cell activation and IgG class switch in absence of any T cell help in a small fraction of naïve WT B cells, and in much larger fraction of B cells from lupus prone TCSle mice, triggering T cell-independent autoantibody production. We also found that CD40L-dependent T cell help can enhance curli/DNA induced autoAbs, prompting future studies to characterize the antigen specificity of these helper T cells. 4) We found that persistent bacteriuria by curli-expressing Uropathogenic E. Coli is linked to flares in SLE patients. These studies suggest commensal biofilms and bacterial amyloids as new therapeutic targets and anti-curli Abs as new biomarker of flares in lupus.