Systemic Lupus Erythematosus (SLE) is an autoimmune disease with a complex pathogenesis, in which environmental triggers act in individuals with a genetic susceptibility to break immunological self-tolerance. Translational and epidemiological studies indicate that patients with SLE are frequently exposed to microbial products and suggest that bacterial infections may promote SLE in predisposed individuals, but the underlying mechanisms remain unknown. We have recently reported that a subset of female patients with SLE, who have asymptomatic persistent bacteriuria, show higher levels of pro-inflammatory markers and disease flares. These patients have high levels of anti-dsDNA antibodies (Abs) that correlate with high levels of Abs against curli/DNA, a bacterial amyloid complexed with bacterial DNA. Curli/DNA is an amyloid produced by Gram-negative bacteria, like UroPathogenic Escherichia coli (UPEC), a frequent cause of bacteriuria and UTI, when they produce biofilms. Bacterial biofilms are structured communities of bacteria that protect bacteria from a hostile environment, including our immune system. We have previously reported that curli/DNA and infections with biofilms accelerate lupus onset in lupus-prone mice and activate immune cells to secrete type I Interferons (IFNs), a cytokine important in lupus pathogenesis. We had also shown that exposure to bacterial biofilms activate murine inflammatory dendritic cells to up-regulate costimulatory molecules and pro-inflammatory cytokines, suggesting an important molecular step in the triggering of lupus flares. We report here that human primary monocytes-derived dendritic cells recognize in vitro bacterial biofilms from E. coli and their best studied PAMP, the amyloid curli/DNA, and activate a pro-inflammatory program. These results establish the human relevance for the investigations of the role of bacterial biofilms in the pathogenesis of SLE.