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Inflammation-induced impairment of enteric nerve function in nematode-infected mice is macrophage dependent
F Galeazzi1, E M Haapala, N van Rooijen
1Intestinal Diseases Research Programme, Health Sciences Centre, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.
Abstract:
Trichinella spiralis infection in rodents is associated with suppression of ACh release from myenteric plexus that can be mimicked by macrophage-derived cytokines. We verified the presence of a macrophage infiltrate in the intestine during T. spiralis infection and determined the extent to which this cell type is responsible for the neural changes. C57BL/6 mice were infected with 375 T. spiralis larvae by gavage, and the presence of macrophages (F4/80 positive) in the jejunum was determined immunohistochemically. In another experiment, infected mice were treated intravenously with liposomes containing dichloromethylene diphosphonate (clodronate, Cl(2)MDP), which causes apoptosis of macrophages, and killed at postinfection day 6, and jejunal tissues were evaluated for the presence of F4/80-positive cells and for [(3)H]ACh release from the myenteric plexus. Infection caused an infiltration of F4/80-positive cells into the intestinal mucosa, muscle layers, and myenteric plexus region and a significant suppression of ACh release (50%). Depletion of F4/80-positive macrophages using Cl(2)MDP-containing liposomes prevented the suppression in [(3)H]ACh release, identifying macrophages as the cell type involved in the functional impairment of enteric cholinergic nerves.
Insights
Trichinella spiralis infection suppresses acetylcholine (ACh) release in the gut by activating macrophages. Macrophage depletion prevents this neural dysfunction, identifying them as key players in the infection
Area of Science:
- Immunology
- Neurogastroenterology
- Parasitology
Background:
- Trichinella spiralis infection impacts gut function.
- Macrophage-derived cytokines can mimic neural suppression.
- The role of macrophages in T. spiralis-induced neural changes requires clarification.
Purpose of the Study:
- To verify macrophage infiltration during T. spiralis infection.
- To determine if macrophages cause neural changes in the myenteric plexus.
- To investigate the impact of macrophage depletion on acetylcholine release.
Main Methods:
- C57BL/6 mice infected with T. spiralis larvae.
- Immunohistochemistry used to detect F4/80-positive macrophages in jejunum.
- Macrophage depletion via clodronate-liposomes.
- Measurement of [(3)H]ACh release from myenteric plexus.
Main Results:
- T. spiralis infection led to significant infiltration of F4/80-positive macrophages.
- A 50% suppression of ACh release was observed in infected mice.
- Depletion of macrophages prevented the suppression of ACh release.
Conclusions:
- Macrophages infiltrate the jejunum during T. spiralis infection.
- Macrophages are responsible for the suppression of acetylcholine release.
- Macrophage depletion protects enteric cholinergic nerves from functional impairment.