Mast cell production of IL-4 and TNF may be required for protective and pathological responses in gastrointestinal helminth infection

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/Wv) mice were reconstituted with wild-type, tumor necrosis factor (TNF)--/-, or interleukin (IL)-4-/- bone marrow (BM) prior to infection with T. spiralis. W/Wv mice reconstituted with TNF--/- or IL-4-/- BM expelled the parasite less efficiently and showed diminished enteropathy, whereas protective responses were normal in W/Wv mice reconstituted with wild-type BM and were accompanied by intestinal pathology. MC responses were reduced in W/Wv mice reconstituted with IL-4-/- BM and to a lesser extent when reconstituted with TNF--/-. 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.