Genome-Derived Cytosolic DNA Mediates Type I Interferon-Dependent Rejection of B Cell Lymphoma Cells

被引：147

作者：

Shen, Yu J. ^{[1
,2
,3
]}

Le Bert, Nina ^{[1
,2
]}

Chitre, Anuja A. ^{[1
,2
]}

Koo, Christine Xing'Er ^{[3
,4
]}

Nga, Xing H. ^{[1
,2
]}

Ho, Samantha S. W. ^{[1
,2
]}

Khatoo, Muznah ^{[1
,2
]}

Tan, Nikki Y. ^{[1
,2
]}

Ishii, Ken J. ^{[4
,5
]}

Gasser, Stephan ^{[1
,2
,3
]}

机构：

[1] Natl Univ Singapore, Immunol Programme, Ctr Life Sci, Singapore 117456, Singapore

[2] Natl Univ Singapore, Dept Microbiol, Ctr Life Sci, Singapore 117456, Singapore

[3] Natl Univ Singapore, NUS Grad Sch Integrat Sci & Engn, Singapore 117456, Singapore

[4] Natl Inst Biomed Innovat NIBIO, Lab Adjuvant Innovat, Ibaraki, Osaka 5670085, Japan

[5] Osaka Univ, WPI Immunol Frontier Res Ctr iFREC, Lab Vaccine Sci, Suita, Osaka 5650871, Japan

来源：

Cell Reports | 2015年 / 11卷 / 03期

基金：

新加坡国家研究基金会;

关键词：

DOUBLE-STRAND BREAKS; ADAPTIVE IMMUNITY; DAMAGE RESPONSE; R-LOOPS; INSTABILITY; REPLICATION; INNATE; CANCER; INITIATION; STABILITY;

D O I：

10.1016/j.celrep.2015.03.041

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：460 / 473

页数：14

共 36 条

[31] R-loops and nicks initiate DNA breakage and genome instability in non-growing Escherichia coli [J].