title: 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.affiliation: The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Yikun
authors.initials: Y
authors.lastname: Yao
authors.forename: Yalong
authors.initials: Y
authors.lastname: Wang
authors.forename: Fuxiang
authors.initials: F
authors.lastname: Chen
authors.forename: Yin
authors.initials: Y
authors.lastname: Huang
authors.forename: Shu
authors.initials: S
authors.lastname: Zhu
authors.forename: Qibin
authors.initials: Q
authors.lastname: Leng
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
authors.forename: Yufang
authors.initials: Y
authors.lastname: Shi
authors.forename: Youcun
authors.initials: Y
authors.lastname: Qian
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D049109:Cell Proliferation; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D058847:Inflammasomes / Q000378:metabolism; D007370:Interferon Type I / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000472:pathogenicity; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein
chemical_list: D002352:Carrier Proteins; D015395:Histocompatibility Antigens Class I; D058847:Inflammasomes; D007370:Interferon Type I; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C549161:NLRC5 protein, mouse; C453881:NLRP3 protein, human