期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 202, 期 10, 页码 1333-1339出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20051654
关键词
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Deoxyribonuclease ( DNase) II in macrophages cleaves the DNA of engulfed apoptotic cells and of nuclei expelled from erythroid precursor cells. DNase II - deficient mouse embryos accumulate undigested DNA in macrophages, and die in feto because of the activation of the interferon beta(IFN beta) gene. Here, we found that the F4/80-positive macrophages in DNase II-/- fetal liver specifically produce a set of cytokines such as IFN beta, TNF alpha, and CXCL10. Whereas, IFN-inducible genes (2'5'-oligo(A) synthetase, IRF7, and ISG15) were expressed not only in macrophages but also in other F4/ 80- negative cells. When DNase II-/- macrophages or embryonal fibroblasts engulfed apoptotic cells, they expressed the IFN beta and CXCL10 genes. The ablation of Toll-like receptor (TLR) 3 and 9, or their adaptor molecules (MyD88 and TRIF), had no effect on the lethality of the DNase II-/- mice. These results indicate that there is a TLR-independent sensing mechanism to activate the innate immunity for the endogenous DNA escaping lysosomal degradation.
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