| First Author | Okabe Y | Year | 2005 |
| Journal | J Exp Med | Volume | 202 |
| Issue | 10 | Pages | 1333-9 |
| PubMed ID | 16301743 | Mgi Jnum | J:118847 |
| Mgi Id | MGI:3700461 | Doi | 10.1084/jem.20051654 |
| Citation | Okabe Y, et al. (2005) Toll-like receptor-independent gene induction program activated by mammalian DNA escaped from apoptotic DNA degradation. J Exp Med 202(10):1333-9 |
| abstractText | 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 (IFNbeta) gene. Here, we found that the F4/80-positive macrophages in DNase II(-/-) fetal liver specifically produce a set of cytokines such as IFNbeta, TNFalpha, 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 IFNbeta 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. |
