NLRC5 regulates MHC class I antigen presentation in host defense against intracellular pathogens.

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.

• Authors: Yikun Yao, Yalong Wang, Fuxiang Chen, Yin Huang, Shu Zhu, Qibin Leng, Hongyan Wang, Yufang Shi, Youcun Qian
• Journal: Cell research (Cell Res) Vol. 22 Issue 5 Pg. 836-47 (May 2012) ISSN: 1748-7838 [Electronic] England
• PMID: 22491475 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• Histocompatibility Antigens Class I
• Inflammasomes
• Interferon Type I
• Intracellular Signaling Peptides and Proteins
• NF-kappa B
• NLR Family, Pyrin Domain-Containing 3 Protein
• NLRC5 protein, mouse
• NLRP3 protein, human

Topics

• Animals
• Antigen Presentation (immunology)
• CD8-Positive T-Lymphocytes (immunology, metabolism)
• Carrier Proteins (metabolism)
• Cell Proliferation
• Histocompatibility Antigens Class I (genetics, metabolism)
• Inflammasomes (metabolism)
• Interferon Type I (metabolism)
• Intracellular Signaling Peptides and Proteins (deficiency, genetics, metabolism)
• Listeria monocytogenes (pathogenicity)
• Lymphocyte Activation
• Mice
• Mice, Knockout
• NF-kappa B (metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein