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Nuclear receptor ERR alpha and coactivator PGC-1 beta are effectors of IFN-gamma-induced host defense.
Nuclear receptor ERR alpha and coactivator PGC-1 beta are effectors of IFN-gamma-induced host defense.
- Source :
-
Genes & development [Genes Dev] 2007 Aug 01; Vol. 21 (15), pp. 1909-20. - Publication Year :
- 2007
-
Abstract
- 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 ERR alpha (estrogen-related receptor alpha, NR3B1). Studies with macrophages lacking ERR alpha 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 ERR alpha are susceptible to LM infection, a phenotype that is localized to bone marrow-derived cells. Furthermore, we found that IFN-gamma-induced activation of ERR alpha depends on coactivator PGC-1 beta (peroxisome proliferator-activated receptor gamma coactivator-1 beta), which appears to be a direct target for the IFN-gamma/STAT-1 signaling cascade. Thus, ERR alpha and PGC-1 beta act together as a key effector of IFN-gamma-induced mitochondrial ROS production and host defense.
- Subjects :
- Animals
Base Sequence
Carrier Proteins genetics
DNA genetics
Female
Gene Expression drug effects
In Vitro Techniques
Listeria monocytogenes immunology
Listeria monocytogenes pathogenicity
Macrophage Activation immunology
Macrophages drug effects
Macrophages immunology
Macrophages metabolism
Macrophages microbiology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mitochondria drug effects
Mitochondria metabolism
Models, Biological
RNA-Binding Proteins
Reactive Oxygen Species metabolism
Receptors, Estrogen deficiency
Receptors, Estrogen genetics
Recombinant Proteins
Signal Transduction drug effects
ERRalpha Estrogen-Related Receptor
Carrier Proteins metabolism
Interferon-gamma pharmacology
Macrophage Activation drug effects
Macrophage Activation physiology
Receptors, Estrogen metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0890-9369
- Volume :
- 21
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Genes & development
- Publication Type :
- Academic Journal
- Accession number :
- 17671090
- Full Text :
- https://doi.org/10.1101/gad.1553007