| First Author | Sonoda J | Year | 2007 |
| Journal | Genes Dev | Volume | 21 |
| Issue | 15 | Pages | 1909-20 |
| PubMed ID | 17671090 | Mgi Jnum | J:123419 |
| Mgi Id | MGI:3718283 | Doi | 10.1101/gad.1553007 |
| Citation | Sonoda J, et al. (2007) Nuclear receptor ERR{alpha} and coactivator PGC-1beta are effectors of IFN-{gamma}-induced host defense. Genes Dev 21(15):1909-20 |
| abstractText | Macrophage activation by the proinflammatory cytokine interferon-gamma (IFN-gamma) is a critical component of the host innate response to bacterial pathogenesis. However, the precise nature of the IFN-gamma-induced activation pathway is not known. Here we show using genome-wide expression and chromatin-binding profiling that IFN-gamma induces the expression of many nuclear genes encoding mitochondrial respiratory chain machinery via activation of the nuclear receptor ERRalpha (estrogen-related receptor alpha, NR3B1). Studies with macrophages lacking ERRalpha demonstrate that it is required for induction of mitochondrial reactive oxygen species (ROS) production and efficient clearance of Listeria monocytogenes (LM) in response to IFN-gamma. As a result, mice lacking ERRalpha are susceptible to LM infection, a phenotype that is localized to bone marrow-derived cells. Furthermore, we found that IFN-gamma-induced activation of ERRalpha depends on coactivator PGC-1beta (peroxisome proliferator-activated receptor gamma coactivator-1beta), which appears to be a direct target for the IFN-gamma/STAT-1 signaling cascade. Thus, ERRalpha and PGC-1beta act together as a key effector of IFN-gamma-induced mitochondrial ROS production and host defense. |
