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Cutting Edge: IPSE/alpha-1, a Glycoprotein from Schistosoma mansoni Eggs, Induces IgE-Dependent, Antigen-Independent IL-4 Production by Murine Basophils In Vivo¹

Gabriele Schramm^2,*, Katja Mohrs^2,, Maren Wodrich^*, Michael J. Doenhoff, Edward J. Pearce, Helmut Haas^* and Markus Mohrs^3,

^* Research Center Borstel, Borstel, Germany; Trudeau Institute, Saranac Lake, NY 12983; School of Biological Sciences, University of Wales, Bangor, Wales, United Kingdom; Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104

During infection with the helminth parasite Schistosoma mansoni, the deposition of eggs coincides with the onset of IL-4 production and Th2 development. Although IL-4 is known as a potent inducer of Th2 differentiation, the mechanism by which schistosome eggs induce IL-4 production is not clear. In this study, we demonstrate that the S. mansoni egg Ag (SmEA) induces IgE-dependent IL-4 production by basophils derived from Heligmosomoides polygyrus-infected or OVA/alum-immunized mice in the absence of pathogen-specific IgE. The effect is mediated by the secretory glycoprotein IPSE/alpha-1, because IPSE/alpha-1-depleted SmEA no longer induces cytokine production. Conversely, recombinant IPSE/alpha-1 is sufficient to induce IL-4 production. Importantly, the injection of SmEA or recombinant IPSE/alpha-1 into H. polygyrus-infected 4get/KN2 IL-4 reporter mice rapidly induces the dose-dependent IL-4 production by basophils in the liver, a major site of egg deposition. Thus, IPSE/alpha-1 induces basophils to produce IL-4 even in the absence of Ag-specific IgE.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by funds from the Trudeau Institute, National Institutes of Health Grants AI45666 (to M.M.), AI072296 (to M.M.), and AI32573 (to E.J.P.), and the Deutsche Forschungsgemeinschaft Grants SFB/TRR22 (A12) and GRK 288 (to G.S. and H.H.). Schistosome life stages for these experiments were in part provided by the National Institutes of Allergy and Infectious Diseases Contract NO155270.

² G.S. and K.M. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Markus Mohrs, Trudeau Institute, 154 Algonquin Avenue, Saranac Lake, NY 12983. E-mail address: mmohrs{at}trudeauinstitute.org

⁴ Abbreviations used in this paper: SmEA, Schistosoma mansoni egg Ag; alum, aluminum hydroxide; HEK, human embryonic kidney; Hp, Heligmosomoides polygyrus; WT, wild type.