Sensory Nociceptive Neurons Contribute to Host Protection During Enteric Infection With Citrobacter rodentium

J Infect Dis. 2020 Jun 11;221(12):1978-1988. doi: 10.1093/infdis/jiaa014.

Abstract

Background: Neurons are an integral component of the immune system that functions to coordinate responses to bacterial pathogens. Sensory nociceptive neurons that can detect bacterial pathogens are found throughout the body with dense innervation of the intestinal tract.

Methods: In this study, we assessed the role of these nerves in the coordination of host defenses to Citrobacter rodentium. Selective ablation of nociceptive neurons significantly increased bacterial burden 10 days postinfection and delayed pathogen clearance.

Results: Because the sensory neuropeptide CGRP (calcitonin gene-related peptide) regulates host responses during infection of the skin, lung, and small intestine, we assessed the role of CGRP receptor signaling during C rodentium infection. Although CGRP receptor blockade reduced certain proinflammatory gene expression, bacterial burden and Il-22 expression was unaffected.

Conclusions: Our data highlight that sensory nociceptive neurons exert a significant host protective role during C rodentium infection, independent of CGRP receptor signaling.

Keywords: Citrobacter rodentium; CGRP; TRPV1; nociceptors.

Publication types

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

MeSH terms

  • Animals
  • Calcitonin Gene-Related Peptide / metabolism
  • Calcitonin Gene-Related Peptide Receptor Antagonists / pharmacology
  • Citrobacter rodentium / immunology*
  • Disease Models, Animal
  • Enteric Nervous System / cytology
  • Enteric Nervous System / drug effects
  • Enteric Nervous System / immunology*
  • Enterobacteriaceae Infections / immunology*
  • Enterobacteriaceae Infections / microbiology
  • Host-Pathogen Interactions / drug effects
  • Host-Pathogen Interactions / immunology*
  • Humans
  • Intestinal Mucosa / innervation
  • Intestinal Mucosa / microbiology
  • Intestine, Small / innervation
  • Intestine, Small / microbiology
  • Mice
  • Mice, Knockout
  • Nociceptors / drug effects
  • Nociceptors / immunology*
  • Nociceptors / metabolism
  • Receptors, Calcitonin Gene-Related Peptide / metabolism
  • TRPV Cation Channels / genetics

Substances

  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Receptors, Calcitonin Gene-Related Peptide
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • Calcitonin Gene-Related Peptide