IL-13, IL-4Ralpha, and Stat6 are required for the expulsion of the gastrointestinal nematode parasite Nippostrongylus brasiliensis.

Although IL-4 induces expulsion of the gastrointestinal nematode parasite, Nippostrongylus brasiliensis, from immunodeficient mice, this parasite is expelled normally by IL-4-deficient mice. This apparent paradox is explained by observations that IL-4 receptor alpha chain (IL-4Ralpha)-deficient mice and Stat6-deficient mice fail to expel N. brasiliensis, and a specific antagonist for IL-13, another activator of Stat6 through IL-4Ralpha, prevents worm expulsion. Thus, N. brasiliensis expulsion requires signaling via IL-4Ralpha and Stat6, and IL-13 may be more important than IL-4 as an inducer of the Stat6 signaling that leads to worm expulsion. Additional observations made in the course of these experiments demonstrate that Stat6 signaling is not required for IL-4 enhancement of IgG1 production and actually inhibits IL-4-induction of mucosal mastocytosis.

IFN inhibits inflammatory responses and protective immunity in mice infected with the nematode parasite, Nippostrongylus brasiliensis.

Mice infected with the gastrointestinal nematode parasite Nippostrongylus brasiliensis (Nb) develop responses associated with enhanced production of IL-4 (increased serum IgE levels and intestinal mucosal mastocytosis) and IL-5 (tissue and peripheral blood eosinophilia). The antagonistic effects of IFN on IL-4-mediated responses prompted an examination of the effects of IFN on the host response to Nb. Treatment with rIFN-alpha and rIFN-gamma induced a marked increase in parasite egg production (fecundity) in BALB/c mice infected with Nb and delayed intestinal expulsion of adult worms. Treatment with rIFN-alpha or rIFN-gamma also inhibited the rise in peripheral blood eosinophilia that follows inoculation with Nb, and the intensity of pulmonary perivascular tissue eosinophilia. However, Nb-induced increases in serum IgG levels and intestinal mastocytosis were only temporarily delayed by IFN. Induction of endogenous IFN production by injection of fixed Brucella abortus into mice infected with Nb also resulted in an increased worm fecundity and delayed adult worm expulsion. These effects were ablated when mice given Brucella abortus also received injections of neutralizing anti-IFN antibodies. Thus, IFN inhibit host protective immunity to Nb, perhaps by interfering with the production and effects of Th2 cytokines.