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

Description

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. Author summary The intestine is the first barrier to fight non-commensal bacteria ingested along with the food. The innate immune system is the main mean mounted by the gut lining in response to ill-causing bacteria to avoid detrimental impact. Intestinal cells produce chlorine bleach and antimicrobial peptides that destroy exogenous bacteria. Here, we identified and characterized a new mechanism of gut defense that occurs rapidly after ingestion of exogenous bacteria. We found that the enteroendocrine cells perceive the presence of chlorine bleach in the lumen thanks to a sensor. This sensor promotes a calcium flux within enteroendo-crine cells that allows the release of a hormone. This hormone acts locally on the visceral muscle surrounding the intestine by provoking its strong contractions (or spasms). We show that these strong but brief visceral contractions are helping to the quick expulsion of PLOS Pathogens | https://doi.org/10.1371/journal.ppat.

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