The DH31/CGRP enteroendocrine peptide triggers intestinal contractions favoring the elimination of opportunistic bacteria

PLoS Pathog. 2018 Sep 4;14(9):e1007279. doi: 10.1371/journal.ppat.1007279. eCollection 2018 Sep.


The digestive tract is the first organ affected by the ingestion of foodborne bacteria. While commensal bacteria become resident, opportunistic or virulent bacteria are eliminated from the gut by the local innate immune system. Here we characterize a new mechanism of defense, independent of the immune system, in Drosophila melanogaster. We observed strong contractions of longitudinal visceral muscle fibers for the first 2 hours following bacterial ingestion. We showed that these visceral muscle contractions are induced by immune reactive oxygen species (ROS) that accumulate in the lumen and depend on the ROS-sensing TRPA1 receptor. We then demonstrate that both ROS and TRPA1 are required in a subset of anterior enteroendocrine cells for the release of the DH31 neuropeptide which activates its receptor in the neighboring visceral muscles. The resulting contractions of the visceral muscles favors quick expulsion of the bacteria, limiting their presence in the gut. Our results unveil a precocious mechanism of defense against ingested opportunistic bacteria, whether they are Gram-positive like Bacillus thuringiensis or Gram-negative like Erwinia carotovora carotovora. Finally, we found that the human homolog of DH31, CGRP, has a conserved function in Drosophila.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Bacillus thuringiensis / pathogenicity
  • Calcitonin Gene-Related Peptide / physiology*
  • Drosophila Proteins / physiology*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / microbiology
  • Drosophila melanogaster / physiology
  • Female
  • Food Microbiology
  • Foodborne Diseases / microbiology
  • Foodborne Diseases / physiopathology
  • Gastrointestinal Microbiome / physiology*
  • Gastrointestinal Tract / microbiology*
  • Gastrointestinal Tract / physiology*
  • Humans
  • Immunity, Innate
  • Insect Hormones / physiology*
  • Ion Channels
  • Lactobacillus plantarum / pathogenicity
  • Muscle Contraction / physiology
  • Opportunistic Infections / microbiology
  • Opportunistic Infections / physiopathology
  • Opportunistic Infections / prevention & control
  • Pectobacterium carotovorum / pathogenicity
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • TRPA1 Cation Channel / physiology


  • Dh31 protein, Drosophila
  • Drosophila Proteins
  • Insect Hormones
  • Ion Channels
  • Reactive Oxygen Species
  • TRPA1 Cation Channel
  • TrpA1 protein, Drosophila
  • Calcitonin Gene-Related Peptide

Grant support

This work was supported from Région Provence Alpes Côte d'Azur, Département des Alpes-Maritimes and the Agence Nationale de la Recherche (ANR-13-CESA-0003-01 to AG). RL was supported by a grant from the Ministère de l’Education Nationale, de l’Enseignement Supérieur et de la Recherche. RJ was supported by a grant from the association AZM & SAADE. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.