Molecular characterization of an interleukin-4-inducing factor from Schistosoma mansoni eggs.
The eggs of the parasitic trematode Schistosoma mansoni are powerful inducers of a T helper type 2 (Th2) immune response and immunoglobulin E (IgE) production. S. mansoni egg extract (SmEA) stimulates human basophils to rapidly release large amounts of interleukin (IL)-4, the key promoter of a Th2 response. Here we show purification and sequence of the IL-4-inducing principle of S. mansoni eggs (IPSE). Stimulation studies with human basophils using SmEA fractions and natural and recombinant IPSE as well as neutralization and immunodepletion studies using antibodies to recombinant IPSE demonstrate that IPSE is the bioactive principle in SmEA leading to activation of basophils and to expression of IL-4 and IL-13. Regarding the mechanism of action, blot analysis showed that IPSE is an IgE-binding factor, suggesting that it becomes effective via cross-linking receptor-bound IgE on basophils. Immunohistology revealed that IPSE is enriched in and secreted from the subshell area of the schistosome egg. We conclude from these data that IPSE may be an important parasite-derived component for skewing the immune response toward Th2.
Schramm
Gabriele
G
Forschungszentrum Borstel, D-23845 Borstel, Germany.
Falcone
Franco H
FH
Gronow
Achim
A
Haisch
Karin
K
Mamat
Uwe
U
Doenhoff
Michael J
MJ
Oliveira
Guilherme
G
Galle
Jürgen
J
Dahinden
Clemens A
CA
Haas
Helmut
H
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001483:Base Sequence; D001491:Basophils / Q000378:metabolism / Q000469:parasitology; D015153:Blotting, Western; D002478:Cells, Cultured; D002852:Chromatography, Ion Exchange; D018076:DNA, Complementary / Q000378:metabolism; D019992:Databases as Topic; D004305:Dose-Response Relationship, Drug; D004527:Egg Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D015723:Gene Library; D015801:Helminth Proteins; D006801:Humans; D007150:Immunohistochemistry; D018793:Interleukin-13 / Q000378:metabolism; D007377:Interleukin-3 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism*; D037102:Lectins / Q000378:metabolism; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012550:Schistosoma mansoni / Q000196:embryology / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018076:DNA, Complementary; D004527:Egg Proteins; D015801:Helminth Proteins; C474807:IPSE protein, Schistosoma mansoni; D018793:Interleukin-13; D007377:Interleukin-3; D037102:Lectins; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D015847:Interleukin-4