title: NLRC5 deficiency does not influence cytokine induction by virus and bacteria infections.
abstract: Nucleotide-binding domain and leucine rich repeat containing gene family receptors (NLRs) are cytosolic proteins that respond to a variety of pathogen and host components to induce inflammatory cytokines. NLRC5 is a recently identified member of the NLR family that has been implicated in positive and negative regulation of antiviral innate immune responses. To clarify whether NLRC5 controls antiviral innate immunity in vivo, we generated NLRC5-deficient mice. Macrophages and dendritic cells derived from NLRC5-deficient mice induced relatively normal levels of IFN-β, IL-6, and TNF-α after treatment with RNA viruses, DNA viruses, and bacteria. The serum cytokine levels after polyinosinic-polycytidylic acid infection were also comparable between control and NLRC5-deficient mice. NLRC5 overexpression promoted IL-1β production via caspase-1, suggesting that NLRC5 constitutes an inflammasome. However, there was no reduction of IL-1β in NLRC5-deficient cells in response to known inflammasome activators, suggesting that NLRC5 controls IL-1β production through an unidentified pathway. These findings indicate that NLRC5 is dispensable for cytokine induction in virus and bacterial infections under physiologic conditions.
authors.affiliation: Laboratory of Host Defense, World Premier International Immunology Frontier Research Center, Osaka University, Osaka, Japan.
authors.forename: Himanshu
authors.initials: H
authors.lastname: Kumar
authors.forename: Surya
authors.initials: S
authors.lastname: Pandey
authors.forename: Jian
authors.initials: J
authors.lastname: Zou
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Kumagai
authors.forename: Ken
authors.initials: K
authors.lastname: Takahashi
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Taro
authors.initials: T
authors.lastname: Kawai
mesh_terms: D000818:Animals; D001717:Birds; D020170:Caspase 1 / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009521:Newcastle Disease / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D010641:Phenotype; D012481:Salmonella Infections, Animal / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D014406:Tularemia / Q000276:immunology* / Q000382:microbiology / Q000821:virology
chemical_list: D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; C549161:NLRC5 protein, mouse; D020170:Caspase 1