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Abstract Circulating cell-free DNA in inflamed tissues contains different forms of DNA, including extrachromosomal circular DNA (eccDNA). The role of DNA topology in innate immune sensing remains poorly understood. Here we show that circular DNA is a potent ligand for human plasmacytoid dendritic cells (pDCs) and that the cathelicidin host defense peptide LL37 selectively enhances circular DNA-induced activation.
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