Evidence for neuromodulation of enteropathogen invasion in the intestinal mucosa

Kristin L. Schreiber, Lisa D. Price, David R. Brown

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

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-HT3 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.

Original languageEnglish (US)
Pages (from-to)329-337
Number of pages9
JournalJournal of Neuroimmune Pharmacology
Volume2
Issue number4
DOIs
StatePublished - Dec 2007

Bibliographical note

Funding Information:
Acknowledgments The authors thank Dr. Mark Lyte (Dept. of Pharmacy Practice, Texas Tech University Health Sciences Center, Lubbock, TX) for invaluable technical advice. The authors also are grateful to Melissa Casey for excellent technical assistance. This work was supported in part by National Institutes of Health/ National Institute on Drug Abuse grant R01 DA-10200.

Keywords

  • Enteric nervous system
  • Host-pathogen interaction
  • Salmonella typhimurium DT104
  • Small intestine
  • Swine

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