Proteins secreted by the parasitic nematode Nippostrongylus brasiliensis act as adjuvants for Th2 responses

Infections with parasitic helminths such as Nippostronglyus brasiliensis in duce dominant type 2 responses from antigen-specific T helper cells. The po tency of the Th2 bias can also drive Th2 responses to bystander antigens in troduced at the same time as infection. We now report that the Th2-promotin g effect of infection can be reproduced with soluble N. brasiliensis excret ory-secretory proteins (NES) released by adult parasites in vitro. Immuniza tion of BALB/c mice with NES results in the production of IL-4 with elevate d total serum IgE and specific IgG1 antibodies. NES is also able to stimula te IL-4 and polyclonal IgE production in other mouse strains (C59BL/6, B10. D2, CBA). These features are seen whether NES is administered without adjuv ant as soluble protein in phosphate-buffered saline or with complete Freund 's adjuvant which normally favors Th1 responses. Thus, NES possesses intrin sic adjuvanticity. Moreover, co-administration of hen egg lysozyme (HEL) wi th NES in the absence of other adjuvants results in generation of MEL-speci fic lymphocyte proliferation, IL-4 release and IgG1 antibody responses, doc umenting that NES can act as an adjuvant for third-party antigens. Proteina se K digestion or heat treatment of NES before immunization abolished the I L-4-stimulating activity, indicating that the factors acting to promote Th2 induction are proteins secreted by the adult parasite.