Innate Immunity in the C. elegans Intestine Is Programmed by a Neuronal Regulator of AWC Olfactory Neuron Development

Cell Rep. 2020 Apr 7;31(1):107478. doi: 10.1016/j.celrep.2020.03.042.


Olfactory neurons allow animals to discriminate nutritious food sources from potential pathogens. From a forward genetic screen, we uncovered a surprising requirement for the olfactory neuron gene olrn-1 in the regulation of intestinal epithelial immunity in Caenorhabditis elegans. During nematode development, olrn-1 is required to program the expression of odorant receptors in the AWC olfactory neuron pair. Here, we show that olrn-1 also functions in AWC neurons in the cell non-autonomous suppression of the canonical p38 MAPK PMK-1 immune pathway in the intestine. Low activity of OLRN-1, which activates the p38 MAPK signaling cassette in AWC neurons during larval development, also de-represses the p38 MAPK PMK-1 pathway in the intestine to promote immune effector transcription, increased clearance of an intestinal pathogen, and resistance to bacterial infection. These data reveal an unexpected connection between olfactory receptor development and innate immunity and show that anti-pathogen defenses in the intestine are developmentally programmed.

Keywords: AWC neurons; C. elegans; OLRN-1; immune homeostasis; intestinal immunity; olfactory neuron development; pathogen resistance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / immunology
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / immunology
  • Caenorhabditis elegans Proteins / metabolism*
  • Immunity, Innate / genetics
  • Immunity, Innate / immunology*
  • MAP Kinase Signaling System
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mitogen-Activated Protein Kinases / immunology
  • Mitogen-Activated Protein Kinases / metabolism
  • Neurogenesis
  • Olfactory Receptor Neurons / metabolism
  • Receptors, Odorant / metabolism
  • Smell
  • Transcription Factors / metabolism
  • p38 Mitogen-Activated Protein Kinases / immunology
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Caenorhabditis elegans Proteins
  • Membrane Proteins
  • OLRN-1 protein, C elegans
  • Receptors, Odorant
  • Transcription Factors
  • Mitogen-Activated Protein Kinases
  • Pmk-1 protein, C elegans
  • p38 Mitogen-Activated Protein Kinases