Evidence for neuromodulation of enteropathogen invasion in the intestinal mucosa.
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.
Graduate Program in Neuroscience, University of Minnesota, 1988 Fitch Avenue, St. Paul, MN 55108-6010, USA.
Kristin L
KL
Schreiber
Lisa D
LD
Price
David R
DR
Brown
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D017615:Enteric Nervous System / Q000187:drug effects / Q000276:immunology / Q000382:microbiology*; D054308:Enteropathogenic Escherichia coli / Q000187:drug effects / Q000276:immunology; D005260:Female; D007082:Ileum / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D008297:Male; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000276:immunology*; D018377:Neurotransmitter Agents / Q000494:pharmacology / Q000502:physiology; D012481:Salmonella Infections, Animal / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology; D019779:Salmonella enterica / Q000472:pathogenicity; D013552:Swine
D000900:Anti-Bacterial Agents; D018377:Neurotransmitter Agents