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Updated: Apr 15, 2026

Stimulation of Cytoplasmic DNA Sensing Pathways In Vitro and In Vivo
Published on: September 18, 2014
Genome-derived cytosolic DNA mediates type I interferon-dependent rejection of B cell lymphoma cells
Yu J Shen1, Nina Le Bert2, Anuja A Chitre2
1Immunology Programme and Department of Microbiology, Centre for Life Sciences, National University of Singapore, Singapore 117456, Singapore; NUS Graduate School for Integrative Sciences & Engineering, National University of Singapore, Singapore 117456, Singapore.
Abstract:
The DNA damage response (DDR) induces the expression of type I interferons (IFNs), but the underlying mechanisms are poorly understood. Here, we show the presence of cytosolic DNA in different mouse and human tumor cells. Treatment of cells with genotoxic agents increased the levels of cytosolic DNA in a DDR-dependent manner. Cloning of cytosolic DNA molecules from mouse lymphoma cells suggests that cytosolic DNA is derived from unique genomic loci and has the potential to form non-B DNA structures, including R-loops. Overexpression of Rnaseh1, which resolves R-loops, reduced the levels of cytosolic DNA, type I Ifn transcripts, and type I IFN-dependent rejection of lymphoma cells. Live-cell imaging showed a dynamic contact of cytosolic DNA with mitochondria, an important organelle for innate immune recognition of cytosolic nucleotides. In summary, we found that cytosolic DNA is present in many tumor cells and contributes to the immunogenicity of tumor cells.
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