Neural change in Trichinella-infected mice is MHC II independent and involves M-CSF-derived macrophages.
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.
Galeazzi
F
F
Intestinal Diseases Research Program, Health Sciences Center, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.
Lovato
P
P
Blennerhassett
P A
PA
Haapala
E M
EM
Vallance
B A
BA
Collins
S M
SM
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002799:Cholinergic Fibers / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology*; D015870:Gene Expression / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000469:parasitology; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D007583:Jejunum / Q000276:immunology / Q000294:innervation / Q000469:parasitology; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000502:physiology; D009154:Mutation / Q000276:immunology; D009197:Myenteric Plexus / Q000166:cytology / Q000276:immunology / Q000469:parasitology; D012333:RNA, Messenger; D013047:Specific Pathogen-Free Organisms; D014234:Trichinella; D014235:Trichinellosis / Q000276:immunology*; D014316:Tritium
D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D012333:RNA, Messenger; D014316:Tritium; D015847:Interleukin-4; D016173:Macrophage Colony-Stimulating Factor; D000109:Acetylcholine