Microbial Colonization Activates an Immune Fight-and-Flight Response via Neuroendocrine Signaling

Dev Cell. 2019 Apr 8;49(1):89-99.e4. doi: 10.1016/j.devcel.2019.02.001. Epub 2019 Feb 28.

Abstract

The ability to distinguish harmful and beneficial microbes is critical for the survival of an organism. Here, we show that bloating of the intestinal lumen of Caenorhabditis elegans caused by microbial colonization elicits a microbial aversion behavior. Bloating of the intestinal lumen also activates a broad innate immune response, even in the absence of bacterial pathogens or live bacteria. Neuroendocrine pathway genes are upregulated by intestinal bloating and are required for microbial aversion behavior. We propose that microbial colonization and bloating of the intestine may be perceived as a danger signal that activates an immune fight-and-flight response. These results reveal how inputs from the intestine can aid in the recognition of a broad range of microbes and modulate host behavior via neuroendocrine signaling.

Keywords: C. elegans; daf-7; defecation motor program; eat-2; innate immunity; microbial colonization; neuroendocrine; npr-1; pathogen avoidance behavior; unc-25.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bacteria / genetics
  • Bacteria / pathogenicity
  • Behavior, Animal / physiology
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / immunology
  • Caenorhabditis elegans / microbiology
  • Caenorhabditis elegans Proteins / genetics*
  • Gastrointestinal Microbiome / genetics
  • Host-Pathogen Interactions / genetics
  • Host-Pathogen Interactions / immunology
  • Immunity, Innate / genetics*
  • Intestines / immunology
  • Intestines / microbiology
  • Neurosecretory Systems / immunology
  • Neurosecretory Systems / microbiology
  • Neurosecretory Systems / physiology*
  • Pseudomonas aeruginosa / genetics
  • Pseudomonas aeruginosa / pathogenicity
  • Receptors, Neuropeptide Y / genetics*
  • Signal Transduction / genetics

Substances

  • Caenorhabditis elegans Proteins
  • NPR-1 protein, C elegans
  • Receptors, Neuropeptide Y