FC-EPSILON-RI-DEFICIENT MICE INFECTED WITH SCHISTOSOMA-MANSONI MOUNT NORMAL TH2-TYPE RESPONSES WHILE DISPLAYING ENHANCED LIVER PATHOLOGY

The IgE/Fc epsilon RI interaction is postulated to play an important r ole in resistance to helminths both at the level of anti-parasitic eff ector cell function and in the initiation of Th2 responses through IL- 4 produced by Fc epsilon RI+ non-B, non-T (NBNT) cells. To formally ev aluate the role of IgE/Fc epsilon RI signaling in the host response to helminths we studied Schistosoma mansoni infection in Fc epsilon RI k nockout (KO) mice, Infected wild-type (wt) and KO animals showed compa rable adult worm and tissue egg burdens, arguing against a role for Fc epsilon RI in host resistance, Significantly, NBNT cells from infecte d KO, in contrast to wt animals, did not secrete IL-4 when stimulated with anti-IgE Ab or soluble parasite Ag, Nevertheless, serum IgE level s and Th2 cytokine production profiles were comparable in both strains of mice, demonstrating that the Ag-dependent stimulation of IL-4 secr etion by NBNT cells is not essential for helminth-induced Th2 differen tiation, However, when stimulated with low Ag doses, splenocytes from infected Fc epsilon RI-deficient mice produced less IL-4 in vitro than similar cultures from infected wt animals, an effect attributable to their defective NBNT cell function, Moreover, infected KO mice showed enhanced egg granuloma formation and hepatic fibrosis, revealing that the IgE/Fc epsilon RI interaction, while not essential for Th2 respons e development or resistance to primary infection, plays a significant role in down-regulating host pathology.