Proteins secreted by the parasitic nematode Nippostrongylus brasiliensis act as adjuvants for Th2 responses.
Infections with parasitic helminths such as Nippostronglyus brasiliensis induce dominant type 2 responses from antigen-specific T helper cells. The potency of the Th2 bias can also drive Th2 responses to bystander antigens introduced at the same time as infection. We now report that the Th2-promoting effect of infection can be reproduced with soluble N. brasiliensis excretory-secretory proteins (NES) released by adult parasites in vitro. Immunization of BALB/c mice with NES results in the production of IL-4 with elevated total serum IgE and specific IgG1 antibodies. NES is also able to stimulate IL-4 and polyclonal IgE production in other mouse strains (C57BL/6, B10.D2, CBA). These features are seen whether NES is administered without adjuvant as soluble protein in phosphate-buffered saline or with complete Freund's adjuvant which normally favors Th1 responses. Thus, NES possesses intrinsic adjuvanticity. Moreover, co-administration of hen egg lysozyme (HEL) with NES in the absence of other adjuvants results in generation of HEL-specific lymphocyte proliferation, IL-4 release and IgG1 antibody responses, documenting that NES can act as an adjuvant for third-party antigens. Proteinase K digestion or heat treatment of NES before immunization abolished the IL-4-stimulating activity, indicating that the factors acting to promote Th2 induction are proteins secreted by the adult parasite.
Holland
M J
MJ
Institute of Cell, Animal and Population Biology, University of Edinburgh, GB.
Harcus
Y M
YM
Riches
P L
PL
Maizels
R M
RM
D000276:Adjuvants, Immunologic; D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D005838:Genotype; D015801:Helminth Proteins / Q000276:immunology* / Q000378:metabolism; D007114:Immunization / Q000379:methods; D007073:Immunoglobulin E / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009559:Nippostrongylus / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018418:Th2 Cells / Q000276:immunology* / Q000469:parasitology
D000276:Adjuvants, Immunologic; D000947:Antigens, Helminth; D015801:Helminth Proteins; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma