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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.

Authors :
Sonoda J
Laganière J
Mehl IR
Barish GD
Chong LW
Li X
Scheffler IE
Mock DC
Bataille AR
Robert F
Lee CH
Giguère V
Evans RM
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.

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