IFN-gamma-independent effects of IL-12 during intestinal nematode infection.
Expulsion of the gastrointestinal nematode Trichinella spiralis is associated with a pronounced mastocytosis mediated by a Th2-type response involving IL-4, IL-10, and IL-13. When exogenous rIL-12 was administered to T. spiralis-infected NIH mice, this resulted in significant suppression of intestinal mast cell responses, delayed worm expulsion, increased muscle larvae burdens, and a transient, but significant decrease in early Th2 cytokine secretion. rIL-12 treatment also altered chemokine expression in the jejunal mucosa. The effects of exogenous IL-12 administration were largely independent of IFN-gamma as shown by rIL-12 treatment of IFN-gamma knockout mice. Hence, IL-12 may play a significant biological role as a direct negative regulator of intestinal Th2 responses and may act to promote the survival of intestinal parasites in vivo also in the absence of IFN-gamma.
D000818:Animals; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D005260:Female; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000378:metabolism; D018664:Interleukin-12 / Q000008:administration & dosage / Q000502:physiology*; D018793:Interleukin-13 / Q000096:biosynthesis / Q000378:metabolism; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D007411:Intestinal Diseases, Parasitic / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008297:Male; D008415:Mastocytosis / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000276:immunology / Q000469:parasitology; D019707:Receptors, Chemokine / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000008:administration & dosage; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D017160:Trichinella spiralis / Q000254:growth & development / Q000276:immunology*; D014235:Trichinellosis / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D018925:Chemokines; D016207:Cytokines; D018793:Interleukin-13; D019707:Receptors, Chemokine; D011994:Recombinant Proteins; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma