A Crystallin Fold in the Interleukin-4-inducing Principle of Schistosoma mansoni Eggs (IPSE/α-1) Mediates IgE Binding for Antigen-independent Basophil Activation

Abstract

Background:The interleukin-4-inducing principle from Schistosoma mansoni eggs (IPSE/␣-1) triggers basophils to release interleukin-4 and interleukin-13 in an IgE-dependent but antigen-independent way. Results: Structural analysis identified IPSE/␣-1 as a new member of the ␤␥-crystallin superfamily with a unique IgE-binding loop. Conclusion: IPSE/␣-1 activates basophils via IgE-binding crystallin folds. Significance: Schistosomes use unique mechanisms to manipulate the host's immune response.

Antigenic cross‐reactivity between Schistosoma mansoni and peanut: a role for cross‐reactive carbohydrate determinants (CCDs) and implications for the hygiene hypothesis

“…The molecule also binds IgG to some extent, also in a ‘non‐specific’ manner (i.e. by a mechanism that does not involve the immunoglobulin's antigen‐binding site), but with a fourfold lower affinity than IgE . This immunologically non‐specific interaction has previously been shown not to account for the interaction of the rabbit IgG antibodies with IPSE/ α ‐1, and in this study also it can be seen that IgG in the anti‐ κ ‐5 antiserum used in Fig.…”

“…IPSE/ α ‐1 has been identified as a factor in SmSEA capable of inducing the release of IL‐4 from basophils by interacting with IgE on the surface of the cells, albeit not in an antigenically specific manner . Further reports on IPSE/ α ‐1 indicate that a nuclear localization signal is present in its amino acid sequence .…”

“…Further reports on IPSE/ α ‐1 indicate that a nuclear localization signal is present in its amino acid sequence . IPSE/ α ‐1 expression has been reported to be restricted to the egg stage of S. mansoni and the molecule has recently been identified as belonging to the protein superfamily of βγ crystallins . The molecule also binds IgG to some extent, also in a ‘non‐specific’ manner (i.e.…”

Interleukin-4 signaling plays a major role in urogenital schistosomiasis-associated bladder pathogenesis

“…The major sources of IL-4 have also been shown to include other sources beyond the Th2 cells themselves [14]. Parasite egg crude extract has been shown to stimulate enormous IL-4 release from basophils [2, 15], mast cells and other non-T-cell, non-B-cell populations [16], which may indeed represent constitutive sources of IL-4, apart from the Th2 cells. Other Fcε receptor negative non-lymphocyte sources of IL-4 have also been reported [17, 18].…”

“…Other Fcε receptor negative non-lymphocyte sources of IL-4 have also been reported [17, 18]. The most abundant IL-4 inducing egg antigen has since been identified and characterized from S. mansoni and S. haematobium [2, 15, 19, 20]. The interleuking-4 inducing principle from Schistosoma eggs (IPSE) binds to IgE on the surface of these non-T-cell sources, inducing massive IL-4 release that subsequently drive type-2 response [2, 15, 19, 20].…”