title: Genome-derived cytosolic DNA mediates type I interferon-dependent rejection of B cell lymphoma cells.
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.
authors: Immunology 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.
authors: Yu J
authors: YJ
authors: Shen
authors: Immunology Programme and Department of Microbiology, Centre for Life Sciences, National University of Singapore, Singapore 117456, Singapore.
authors: Nina
authors: N
authors: Le Bert
authors: Immunology Programme and Department of Microbiology, Centre for Life Sciences, National University of Singapore, Singapore 117456, Singapore.
authors: Anuja A
authors: AA
authors: Chitre
authors: NUS Graduate School for Integrative Sciences & Engineering, National University of Singapore, Singapore 117456, Singapore; Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation (NIBIO), 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan.
authors: Christine Xing'Er
authors: CX
authors: Koo
authors: Immunology Programme and Department of Microbiology, Centre for Life Sciences, National University of Singapore, Singapore 117456, Singapore.
authors: Xing H
authors: XH
authors: Nga
authors: Immunology Programme and Department of Microbiology, Centre for Life Sciences, National University of Singapore, Singapore 117456, Singapore.
authors: Samantha S W
authors: SS
authors: Ho
authors: Immunology Programme and Department of Microbiology, Centre for Life Sciences, National University of Singapore, Singapore 117456, Singapore.
authors: Muznah
authors: M
authors: Khatoo
authors: Immunology Programme and Department of Microbiology, Centre for Life Sciences, National University of Singapore, Singapore 117456, Singapore.
authors: Nikki Y
authors: NY
authors: Tan
authors: Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation (NIBIO), 7-6-8 Saito-Asagi, Ibaraki, Osaka 567-0085, Japan; Laboratory of Vaccine Science, WPI Immunology Frontier Research Center (iFREC), Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Ken J
authors: KJ
authors: Ishii
authors: Immunology 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. Electronic address: micsg@nus.edu.sg.
authors: Stephan
authors: S
authors: Gasser
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002460:Cell Line; D003600:Cytosol / Q000276:immunology / Q000378:metabolism; D004247:DNA / Q000276:immunology*; D004249:DNA Damage / Q000276:immunology; D045325:HCT116 Cells; D006801:Humans; D007370:Interferon Type I / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D007370:Interferon Type I; D004247:DNA