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Published on: May 2, 2018
Evidence for neuromodulation of enteropathogen invasion in the intestinal mucosa
Kristin L Schreiber1, Lisa D Price, David R Brown
1Graduate Program in Neuroscience, University of Minnesota, 1988 Fitch Avenue, St. Paul, MN 55108-6010, USA.
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-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.
Insights
Enteric nerves modulate Salmonella internalization in the gut lining. Electrical stimulation boosts bacterial entry, while nerve blockers and specific drugs reduce it, revealing neural control over pathogen interaction.
Area of Science:
- Gastroenterology
- Neuroscience
- Microbiology
Background:
- The intestinal mucosa is heavily innervated and exposed to pathogens.
- Understanding host-pathogen interactions is crucial for gut health.
Purpose of the Study:
- To investigate the role of enteric nerves in modulating the intracellular internalization of multidrug-resistant Salmonella Typhimurium DT104.
- To examine the effects of electrical stimulation and pharmacological agents on Salmonella internalization in porcine ileal tissue.
Main Methods:
- Utilized porcine ileum mucosa-submucosa sheets as a model for human intestine.
- Employed a gentamicin-resistance assay to quantify intracellular Salmonella over 90 minutes.
- Assessed the impact of cytochalasin D, dithiothreitol, transmural electrical stimulation, saxitoxin, lidocaine, phentolamine, and tropisetron.
Main Results:
- Cytochalasin D reduced Salmonella internalization; dithiothreitol decreased mucosal adherence.
- Transmural electrical stimulation increased Salmonella internalization.
- Neuronal blockers (saxitoxin, lidocaine) and receptor ligands (phentolamine, tropisetron) decreased Salmonella internalization.
Conclusions:
- Enteric neural activity significantly modulates the interaction between the intestinal mucosa and pathogenic bacteria.
- Neural pathways and specific receptors play a role in regulating Salmonella entry into intestinal cells.
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