Cutting edge: IPSE/alpha-1, a glycoprotein from Schistosoma mansoni eggs, induces IgE-dependent, antigen-independent IL-4 production by murine basophils in vivo.
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.
Schramm
Gabriele
G
Research Center Borstel, Borstel, Germany.
Mohrs
Katja
K
Wodrich
Maren
M
Doenhoff
Michael J
MJ
Pearce
Edward J
EJ
Haas
Helmut
H
Mohrs
Markus
M
D000818:Animals; D000947:Antigens, Helminth / Q000502:physiology*; D001491:Basophils / Q000276:immunology* / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D004527:Egg Proteins / Q000502:physiology*; D015801:Helminth Proteins / Q000502:physiology*; D006801:Humans; D007073:Immunoglobulin E / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015847:Interleukin-4 / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009961:Orosomucoid / Q000502:physiology; D012550:Schistosoma mansoni / Q000276:immunology*
D000947:Antigens, Helminth; D004527:Egg Proteins; D015801:Helminth Proteins; C474807:IPSE protein, Schistosoma mansoni; D009961:Orosomucoid; D015847:Interleukin-4; D007073:Immunoglobulin E