Cutting edge: IL-4 receptor expression by non-bone marrow-derived cells is required to expel gastrointestinal nematode parasites

Expulsion of two gastrointestinal nematode parasites, Nippostrongylus brasiliensis and Trichinella spiralis, is similar in that both require IL-4R alpha expression, but different in that T cells and mast cells are required for IL-4-induced expulsion of T. spiralis but not N. brasiliensis. To examine the role of IL-4R alpha signaling in immunity to these parasites, we studied worm expulsion in chimeric mice that selectively expressed IL-4R alpha on bone marrow-derived or non-bone marrow-derived cells. N. brasiliensis was expelled by mice that expressed IL-4R alpha only on non-bone marrow-derived cells, but not by mice that expressed IL-4R alpha only on bone marrow-derived cells. Although T. spiralis expulsion required IL-4R alpha expression by both bone marrow and non-bone marrow-derived cells, IL-4 stimulation eliminated the requirement for IL-4R alpha expression by bone marrow-derived cells. Thus, direct IL-4R alpha signaling of nonimmune gastrointestinal cells may be generally required to induce worm expulsion, even when mast cell and T cell responses are also required.