title: LGP2 plays extensive roles in modulating innate immune responses in Ctenopharyngodon idella kidney (CIK) cells.
abstract: LGP2 (laboratory of genetics and physiology 2), RIG-I (retinoic acid inducible gene-I) and MDA5 (melanoma differentiation associated gene 5) constitute the RLR (RIG-I-like receptor) family. LGP2 plays a pivotal role in modulating signaling of RIG-I and MDA5 in innate immune responses. In this study, three representative overexpression vectors were constructed and transfected into C. idella kidney (CIK) cell line to research functional characterizations of CiLGP2 (C. idella LGP2). CiLGP2 overexpression led to the induction of CiRIG-I transcripts. After GCRV challenge, CiLGP2 enhanced CiMDA5 and CiIPS-1 to reinforce the immune response, however, impaired the expression of CiRIG-I. Meanwhile, antiviral activity assays showed that overexpression of CiLGP2 or its domains could inhibit GCRV replication and protect cells from death. Besides, CiLGP2 lingeringly induced CiRIG-I mRNA expression and inhibited CiMDA5 transcripts post poly(I:C) simulation. As a result, CiLGP2 suppressed the RLR-mediated signaling pathway against poly(I:C). Furthermore, CiLGP2 played active roles in RLR signaling response to bacterial PAMPs (LPS and PGN) stimulation. CiLGP2 altered the expression pattern of CiIPS-1 after LPS treatment, while it significantly enhanced the RLR signaling pathway against PGN stimulation. These results collectively suggested that CiLGP2 played a strikingly broad regulation in RLR mediated innate immune responses in C. idella, responding to not only the dsRNA virus or synthetic dsRNA but also bacterial PAMPs, which contribute to the understanding of C. idella LGP2 and RLR signaling pathways. In addition, these results lay a foundation for the further functional mechanism research of LGP2 in fishes.
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Chen
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China.
authors.forename: Chunrong
authors.initials: C
authors.lastname: Yang
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China. Electronic address: su.jianguo@gmail.com.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Su
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
authors.forename: Youliang
authors.initials: Y
authors.lastname: Rao
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
authors.forename: Tianle
authors.initials: T
authors.lastname: Gu
mesh_terms: D000818:Animals; D002347:Carps / Q000235:genetics / Q000276:immunology* / Q000821:virology; D002460:Cell Line; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000276:immunology; D029941:Fish Proteins / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology*; D007668:Kidney / Q000166:cytology / Q000276:immunology* / Q000821:virology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D012087:Reoviridae / Q000276:immunology* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D029941:Fish Proteins; D008070:Lipopolysaccharides; D053487:DEAD-box RNA Helicases
keywords: CIK cells; Grass carp (Ctenopharyngodon idella); Grass carp reovirus; LGP2; RLR pathway