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.
Schreiber
Kristin L
KL
Graduate Program in Neuroscience, University of Minnesota, 1988 Fitch Avenue, St. Paul, MN 55108-6010, USA.
Price
Lisa D
LD
Brown
David R
DR
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