title: Mast cell production of IL-4 and TNF may be required for protective and pathological responses in gastrointestinal helminth infection.
abstract: Expulsion of the gastrointestinal nematode Trichinella spiralis is associated with Th2 responses and intestinal inflammation, which correlate with a marked mast cell (MC) response. To address the role of MC-derived cytokines in the induction of protective responses, WBB6F1-KitW/KitW-v (W/W(v)) mice were reconstituted with wild-type, tumor necrosis factor (TNF)-alpha(-/-), or interleukin (IL)-4(-/-) bone marrow (BM) prior to infection with T. spiralis. W/W(v) mice reconstituted with TNF-alpha(-/-) or IL-4(-/-) BM expelled the parasite less efficiently and showed diminished enteropathy, whereas protective responses were normal in W/W(v) mice reconstituted with wild-type BM and were accompanied by intestinal pathology. MC responses were reduced in W/W(v) mice reconstituted with IL-4(-/-) BM and to a lesser extent when reconstituted with TNF-alpha(-/-). These results suggest that MC-derived IL-4 and TNF may regulate the induction of protective Th2 responses and intestinal inflammation associated with the expulsion of T. spiralis. Significantly, these studies suggest a role for MC-derived cytokines as autocrine growth factors.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, Scotland.
authors.forename: M X
authors.initials: MX
authors.lastname: Ierna
authors.forename: H E
authors.initials: HE
authors.lastname: Scales
authors.forename: K L
authors.initials: KL
authors.lastname: Saunders
authors.forename: C E
authors.initials: CE
authors.lastname: Lawrence
mesh_terms: D000818:Animals; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology*; D007411:Intestinal Diseases, Parasitic / Q000235:genetics / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D018418:Th2 Cells / Q000276:immunology*; D017160:Trichinella spiralis / Q000276:immunology*; D014235:Trichinellosis / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4