Neuronal GPCR NMUR-1 regulates distinct immune responses to different pathogens
Phillip Wibisono,
Shawndra Wibisono,
Jan Watteyne,
Chia-Hui Chen,
Durai Sellegounder,
Isabel Beets,
Yiyong Liu,
Jingru Sun
Affiliations
Phillip Wibisono
Department of Translational Medicine and Physiology, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA, USA
Shawndra Wibisono
Department of Translational Medicine and Physiology, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA, USA
Jan Watteyne
Department of Biology, KU Leuven, Leuven, Belgium
Chia-Hui Chen
Department of Translational Medicine and Physiology, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA, USA
Durai Sellegounder
Department of Translational Medicine and Physiology, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA, USA
Isabel Beets
Department of Biology, KU Leuven, Leuven, Belgium
Yiyong Liu
Department of Translational Medicine and Physiology, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA, USA; Genomics Core, Washington State University, Spokane, WA, USA; Corresponding author
Jingru Sun
Department of Translational Medicine and Physiology, Elson S. Floyd College of Medicine, Washington State University, Spokane, WA, USA; Corresponding author
Summary: A key question in current immunology is how the innate immune system generates high levels of specificity. Using the Caenorhabditis elegans model system, we demonstrate that functional loss of NMUR-1, a neuronal G-protein-coupled receptor homologous to mammalian receptors for the neuropeptide neuromedin U, has diverse effects on C. elegans innate immunity against various bacterial pathogens. Transcriptomic analyses and functional assays reveal that NMUR-1 modulates C. elegans transcription activity by regulating the expression of transcription factors involved in binding to RNA polymerase II regulatory regions, which, in turn, controls the expression of distinct immune genes in response to different pathogens. These results uncover a molecular basis for the specificity of C. elegans innate immunity. Given the evolutionary conservation of NMUR-1 signaling in immune regulation across multicellular organisms, our study could provide mechanistic insights into understanding the specificity of innate immunity in other animals, including mammals.
