Stat6 signaling promotes protective immunity against Trichinella spiralis through a mast cell- and T cell-dependent mechanism

Studies in mice infected with the gastrointestinal nematode parasite Nippos trongylus brasiliensis demonstrated that IL-4/IL-13 activation of Stat6 sup presses development of intestinal mastocytosis and does not contribute to I L-4/IL-13 production, but is still essential for parasite expulsion. Becaus e expulsion of another gastrointestinal nematode, Trichinella spiralis, unl ike N. brasiliensis expulsion, is mast cell dependent, these observations s uggested that T. spiralis expulsion would be Stat6 independent. Instead, we find that Stat6 activation by IL-4/IL-13 is required in T. spiralis-infect ed mice for the mast cell responses that induce worm expulsion and for the cytokine responses that induce intestinal mastocytosis. Furthermore, althou gh lL-4 induces N, brasiliensis expulsion in the absence of B cells, T cell s, and mast cells, mast cells and T cells are required for IL-4 induction o f T spiralis expulsion. Thus, Stat6 signaling is required for host protecti on against N. brasiliensis and T. spiralis but contributes to expulsion of these two worms by different mechanisms. The induction of multiple effector mechanisms by Stat6 signaling provides a way for a cytokine response induc ed by most gastrointestinal nematode parasites to protect against most of t hese parasites, even though different effector mechanisms are required for protection against different nematodes, The Journal of Immunology, 2000, 16 4: 2046-2052.