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Neural change in Trichinella-infected mice is MHC II independent and involves M-CSF-derived macrophages
F Galeazzi1, P Lovato, P A Blennerhassett
1Intestinal Diseases Research Program, Health Sciences Center, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.
Abstract:
Intestinal inflammation due to nematode infection impairs enteric cholinergic nerve function and induces hypercontractility of intestinal muscle. Macrophages have been implicated in the neural changes, but the subpopulation and mechanism involved are unknown. We examined whether macrophages alter nerves by virtue of their ability to activate lymphocytes via major histocompatibility complex (MHC) II-restricted antigen presentation. We also attempted to evaluate the role of macrophage subsets using op/op mice deficient in macrophage colony-stimulating factor (M-CSF). ACh release from the myenteric plexus was measured in MHC II- and M-CSF-deficient (op/op) mice infected with Trichinella spiralis. F4/80-positive macrophages and interleukin-1 beta were constitutively present in op/op and op/? mice but increased only in op/? mice postinfection. After infection, a marked suppression of ACh release occurred only in infected MHC II-deficient and op/? mice. Muscle hypercontractility remained evident in infected op/? mice. Treatment with M-CSF restored macrophage number, and this was accompanied by suppression of cholinergic nerve function during infection. Thus M-CSF plays a critical role in this model by recruiting a subset of macrophages that selectively suppresses enteric neural function.
Insights
Macrophage colony-stimulating factor (M-CSF) recruits specific macrophages that impair nerve function during nematode infections. These macrophages suppress acetylcholine release, impacting gut motility.
Area of Science:
- Immunology
- Neurogastroenterology
- Parasitology
Background:
- Nematode infections cause intestinal inflammation, affecting nerve function and muscle activity.
- Macrophages are implicated in these neural changes, but the specific subset and mechanism remain unclear.
Purpose of the Study:
- To investigate if macrophages alter enteric nerves via MHC II antigen presentation.
- To evaluate the role of macrophage subsets using M-CSF-deficient (op/op) mice.
Main Methods:
- Measuring acetylcholine (ACh) release from the myenteric plexus in infected MHC II- and M-CSF-deficient (op/op) mice.
- Assessing F4/80-positive macrophages and interleukin-1 beta levels postinfection.
- Evaluating muscle hypercontractility.
Main Results:
- MHC II-deficient and op/op mice showed suppressed ACh release after infection.
- Muscle hypercontractility persisted in infected op/op mice.
- M-CSF treatment restored macrophage numbers and suppressed cholinergic nerve function.
Conclusions:
- M-CSF is critical in recruiting a macrophage subset that selectively suppresses enteric neural function during nematode infection.
- This highlights a specific mechanism by which parasitic infections disrupt gut neurophysiology.