Evidence for neuromodulation of enteropathogen invasion in the intestinal mucosa

J Neuroimmune Pharmacol. 2007 Dec;2(4):329-37. doi: 10.1007/s11481-007-9087-x. Epub 2007 Sep 8.


The extensively innervated intestinal mucosa encompasses a vast surface exposed to an array of potentially infectious microorganisms. We investigated the role of enteric nerves in modulating intracellular internalization of a multidrug-resistant Salmonella typhimurium DT104 field isolate in mucosa-submucosa sheets from the porcine ileum, a biomedical model for the human intestine. The effects of transmural electrical stimulation and drugs on intracellular internalization of Salmonella over 90 min was determined by a gentamicin-resistance assay relative to untreated tissues from the same animal serving as controls. The actin inhibitor cytochalasin D reduced internalization of Salmonella, and the mucus-disrupting agent dithiothreitol decreased its mucosal adherence. Transmural electrical stimulation increased, and neuronal conduction blockers saxitoxin and lidocaine decreased Salmonella internalization in stimulated and unstimulated tissues. Furthermore, the alpha-adrenergic/imidazoline receptor ligand phentolamine and the 5-HT(3) receptor antagonist tropisetron decreased internalization in stimulated tissues. Based on these findings, enteric neural activity appears to modulate interactions between the intestinal mucosa and pathogenic bacteria.

Publication types

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

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Drug Resistance, Bacterial
  • Enteric Nervous System / drug effects
  • Enteric Nervous System / immunology
  • Enteric Nervous System / microbiology*
  • Enteropathogenic Escherichia coli / drug effects
  • Enteropathogenic Escherichia coli / immunology
  • Female
  • Ileum / immunology
  • Ileum / metabolism
  • Ileum / microbiology
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology*
  • Male
  • Neuroimmunomodulation / drug effects
  • Neuroimmunomodulation / immunology*
  • Neurotransmitter Agents / pharmacology
  • Neurotransmitter Agents / physiology
  • Salmonella Infections, Animal / drug therapy
  • Salmonella Infections, Animal / immunology
  • Salmonella Infections, Animal / microbiology
  • Salmonella enterica* / pathogenicity
  • Swine


  • Anti-Bacterial Agents
  • Neurotransmitter Agents