NLRC5 regulates MHC class I antigen presentation in host defense against intracellular pathogens
- 10 April 2012
- journal article
- Published by Springer Science and Business Media LLC in Cell Research
- Vol. 22 (5), 836-847
- https://doi.org/10.1038/cr.2012.56
Abstract
NOD-like receptors (NLRs) are a family of intracellular proteins that play critical roles in innate immunity against microbial infection. NLRC5, the largest member of the NLR family, has recently attracted much attention. However, in vitro studies have reported inconsistent results about the roles of NLRC5 in host defense and in regulating immune signaling pathways. The in vivo function of NLRC5 remains unknown. Here, we report that NLRC5 is a critical regulator of host defense against intracellular pathogens in vivo. NLRC5 was specifically required for the expression of genes involved in MHC class I antigen presentation. NLRC5-deficient mice showed a profound defect in the expression of MHC class I genes and a concomitant failure to activate L. monocytogenes-specific CD8+ T cell responses, including activation, proliferation and cytotoxicity, and the mutant mice were more susceptible to the pathogen infection. NLRP3-mediated inflammasome activation was also partially impaired in NLRC5-deficient mice. However, NLRC5 was dispensable for pathogen-induced expression of NF-κB-dependent pro-inflammatory genes as well as type I interferon genes. Thus, NLRC5 critically regulates MHC class I antigen presentation to control intracellular pathogen infection.This publication has 28 references indexed in Scilit:
- NLRC5: a newly discovered MHC class I transactivator (CITA)Microbes and Infection, 2012
- The nucleotide-binding domain of NLRC5 is critical for nuclear import and transactivation activityBiochemical and Biophysical Research Communications, 2012
- Regulation of immune pathways by the NOD-like receptor NLRC5Immunobiology, 2012
- Mitochondrial ROS fuel the inflammasomeCell Research, 2011
- Modulation of experimental autoimmune encephalomyelitis through TRAF3-mediated suppression of interleukin 17 receptor signalingThe Journal of Experimental Medicine, 2010
- A Role for the Human Nucleotide-binding Domain, Leucine-rich Repeat-containing Family Member NLRC5 in Antiviral ResponsesJournal of Biological Chemistry, 2010
- NLR family member NLRC5 is a transcriptional regulator of MHC class I genesProceedings of the National Academy of Sciences of the United States of America, 2010
- NLRC5 Negatively Regulates the NF-κB and Type I Interferon Signaling PathwaysCell, 2010
- The InflammasomesCell, 2010
- The Nucleotide-Binding Oligomerization Domain-Like Receptor NLRC5 Is Involved in IFN-Dependent Antiviral Immune ResponsesThe Journal of Immunology, 2010