title: NPR-9 regulates the innate immune response in Caenorhabditis elegans by antagonizing the activity of AIB interneurons.
abstract: npr-9 encodes a homologue of the gastrin-releasing peptide receptor (GRPR) and is expressed in AIB interneurons. In this study, we investigated the role of NPR-9 in the neuronal control of innate immunity using the model system Caenorhabditis elegans. After exposure to Pseudomonas aeruginosa PA14, npr-9(tm1652) mutants showed resistance to infection, decreased PA14 colonization and increased expression of immunity-related genes. Nematodes overexpressing NPR-9 exhibited increased susceptibility to infection, increased PA14 colonization and reduced expression of immunity-related genes. In nematodes, ChR2-mediated AIB interneuron activation strengthened the innate immune response and decreased PA14 colonization. Overexpression of NPR-9 suppressed the innate immune response and increased PA14 colonization in nematodes with the activation of AIB interneurons mediated by ChR2 or by expressing pkc-1(gf) in AIB interneurons. We, therefore, hypothesize that NPR-9 regulates the innate immune response by antagonizing the activity of AIB interneurons. Furthermore, expression of GRPR, the human homologue of NPR-9, could largely mimic NPR-9 function by regulating innate immunity in nematodes. Our results provide insight into the pivotal role of interneurons in controlling innate immunity and the complex biological functions of GRPRs.
authors.affiliation: Key Laboratory of Developmental Genes and Human Diseases in Ministry of Education, Medical School, Southeast University, Nanjing 210009, China.
authors.forename: Yonglin
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Key Laboratory of Developmental Genes and Human Diseases in Ministry of Education, Medical School, Southeast University, Nanjing 210009, China.
authors.forename: Lingtong
authors.initials: L
authors.lastname: Zhi
authors.affiliation: Key Laboratory of Developmental Genes and Human Diseases in Ministry of Education, Medical School, Southeast University, Nanjing 210009, China.
authors.forename: Qiuli
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Key Laboratory of Developmental Genes and Human Diseases in Ministry of Education, Medical School, Southeast University, Nanjing 210009, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Jing
authors.affiliation: Key Laboratory of Developmental Genes and Human Diseases in Ministry of Education, Medical School, Southeast University, Nanjing 210009, China.
authors.forename: Dayong
authors.initials: D
authors.lastname: Wang
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004843:Epistasis, Genetic; D006801:Humans; D007113:Immunity, Innate; D007395:Interneurons / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D062308:Optogenetics; D011552:Pseudomonas Infections / Q000276:immunology; D011550:Pseudomonas aeruginosa / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; C000619114:NPR-9 protein, C elegans; D043562:Receptors, G-Protein-Coupled