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NPR-9 regulates the innate immune response in Caenorhabditis elegans by antagonizing the activity of AIB interneurons

Cellular & Molecular Immunology volume 15, pages 27–37 (2018)Cite this article

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.

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Acknowledgements

Several nematode strains used in this study were provided by the CGC, which is funded by NIH Office of Research Infrastructure Program (P40 OD010440).

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  1. Yonglin Yu and Lingtong Zhi: These authors contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Developmental Genes and Human Diseases in Ministry of Education, Medical School, Southeast University, Nanjing, 210009, China

    Yonglin Yu, Lingtong Zhi, Qiuli Wu, Lina Jing & Dayong Wang

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Correspondence to Dayong Wang.

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Yu, Y., Zhi, L., Wu, Q. et al. NPR-9 regulates the innate immune response in Caenorhabditis elegans by antagonizing the activity of AIB interneurons. Cell Mol Immunol 15, 27–37 (2018). https://doi.org/10.1038/cmi.2016.8

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