© 2005 Blackwell Publishing Ltd 387 Parasite Immunology , 2004, 26, 387–395 Blackwell Publishing, Ltd. ORIGINAL ARTICLE IL-4 induction by E. multilocularis extract Echinococcus multilocularis metacestode extract triggers human basophils to release interleukin-4 E. AUMÜLLER, 1 G. SCHRAMM, 1 A. GRONOW, 1 K. BREHM, 2 B. F. GIBBS, 3 M. J. DOENHOFF 4 & H. HAAS 1 1 Division of Cellular Allergology, Research Centre Borstel, Borstel, Germany, 2 Institute for Hygiene and Microbiology, University of Würzburg, Würzburg, Germany, 3 Department of Dermatology, University of Lübeck, Lübeck, Germany, 4 School of Biological Sciences, University of Wales, Bangor, UK SUMMARY Infections with parasitic helminths are associated with a T helper 2 (Th2) immune response and IgE production. The underlying mechanism, however, is only partially understood. Recently we have isolated a protein from extracts of Schistosoma mansoni eggs that triggers human basophils from non-sensitized donors to release interleukin-4 (IL-4), the key cytokine of a Th2 response. We called this protein IPSE (for IL-4-inducing principle from Schistosoma mansoni eggs). Supposing that IPSE-like IL-4- inducing activities might be a general principle shared among different helminth species, we investigated extracts from the cestode E. multilocularis for its effect on human basophils. Our results showed that extracts from metacestodes of E. multilocularis cause basophil degranulation, as well as the secretion of histamine, IL-4 and IL-13, in a dose-dependent manner. IgE stripping and resensitization of basophils indicated that the mechanism of IL-4 induction requires the presence of IgE on the cells. Since analogous properties have been demonstrated earlier for IPSE, we think that S. mansoni and E. multilocularis may induce a Th2 response in their hosts via a related mechanism, namely, by the induction of IL-4 release from basophils. Keywords Echinococcus multilocularis, human basophils, interleukin-4 INTRODUCTION Based on their cytokine production, T helper cells can be divided into two spectral phenotypes: T helper type 1 (Th1) and T helper type 2 (Th2) cells. The polarization of the T-helper response towards the Th2 phenotype as well as the switch to IgE synthesis in B cells are both dependent on interleukin-4 (IL-4). Although, during an ongoing immune response, Th2 cells are the major source of IL-4, they are unlikely to provide the early IL-4 needed for their own differentiation from unprimed Th precursor cells. We and others favour basophils as the primary source of early IL-4 (1–3), because they are very efficacious IL-4 producers and can be activated by a wide variety of different stimuli such as allergens, lectins (4,5) and so-called B cell superantigens (6). Previous studies have shown that basophils are the major source of IL-4 and IL-13 among blood mononuclear cells (PBMC) stimulated with antigen (7–9). Helminth infections are typically associated with a Th2- type immune response, an accumulation of mast cells, eosinophils and elevated production of IgE. This indicates that helminths are highly effective Th2 inducers. To investi- gate the IL-4-inducing capacity of parasitic worms, we stimulated human basophils with helminth extracts. Since, in several helminths, the potential to induce a Th2 response was shown to depend on the life cycle stage of the parasite, as is the case in Schistosoma mansoni and Brugia malayi (10,11), the extracts were obtained from life cycle stages that are associated with induction of a Th2 response. Previously, we have observed that soluble egg extracts from the trematode S. mansoni (SmEA) trigger human basophils from non-sensitized donors to release IL-4 (12). The molecule responsible for this effect (IPSE) was characterized and recombinantly expressed in E. coli (13). To elucidate whether IL-4-inducing activities can be also found in other helminth species – possibly as part of an evolutionary conserved Correspondence: Helmut Haas, Cellular Allergology, Research Centre Borstel, Parkallee 22, D-23845 Borstel, Germany (e-mail: hhaas@fz-borstel.de). Received: 4 May 2004 Accepted for publication: 22 January 2005