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Omega-1, a glycoprotein secreted by Schistosoma mansoni eggs, drives Th2 responses.

Everts B, Perona-Wright G, Smits HH, Hokke CH, van der Ham AJ, Fitzsimmons CM, Doenhoff MJ, van der Bosch J, Mohrs K, Haas H, Mohrs M, Yazdanbakhsh M, Schramm G - J. Exp. Med. (2009)

Bottom Line: We report that omega-1, a glycoprotein which is secreted from S. mansoni eggs and present in SEA, is capable of conditioning human monocyte-derived dendritic cells in vitro to drive T helper 2 (Th2) polarization with similar characteristics as whole SEA.Finally, omega-1-depleted SEA displays an impaired capacity for Th2 priming in vitro, but not in vivo, suggesting the existence of additional factors within SEA that can compensate for the omega-1-mediated effects.Collectively, we identify omega-1, a single component of SEA, as a potent inducer of Th2 responses.

View Article: PubMed Central - PubMed

Affiliation: Department of Parasitology, Leiden University Medical Centre, Leiden 2333 ZA, The Netherlands.

ABSTRACT
Soluble egg antigens of the parasitic helminth Schistosoma mansoni (S. mansoni egg antigen [SEA]) induce strong Th2 responses both in vitro and in vivo. However, the specific molecules that prime the development of Th2 responses have not been identified. We report that omega-1, a glycoprotein which is secreted from S. mansoni eggs and present in SEA, is capable of conditioning human monocyte-derived dendritic cells in vitro to drive T helper 2 (Th2) polarization with similar characteristics as whole SEA. Furthermore, using IL-4 dual reporter mice, we show that both natural and recombinant omega-1 alone are sufficient to generate Th2 responses in vivo, even in the absence of IL-4R signaling. Finally, omega-1-depleted SEA displays an impaired capacity for Th2 priming in vitro, but not in vivo, suggesting the existence of additional factors within SEA that can compensate for the omega-1-mediated effects. Collectively, we identify omega-1, a single component of SEA, as a potent inducer of Th2 responses.

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Omega-1 is a major factor in SEA that conditions DCs for Th2 priming but not the only Th2-inducing component present in SEA. (A and B) Monocyte-derived DCs were pulsed for 48 h with 25 µg/ml SEA or 25 µg/ml omega-1–depleted SEA in combination with 100 ng/ml LPS and analyzed for surface expression of maturation markers and IL-12 production as described in the Fig. 2 legend. Error bars represent the mean ± SD of four independent experiments. (C) T cell–polarizing capacity of the conditioned DCs was evaluated as described in the Fig. 1 legend. Depicted are representative plots with percentages indicated. Based on intracellular cytokine staining, the ratio of T cells single positive for either IL-4 or IFN-γ was calculated relative to the control condition. Error bars represent the mean ± SD of five independent experiments. (D) 4get/KN2 mice were injected with recombinant proteins and analyzed as in Fig. 4. Depicted are representative plots with percentages indicated and the combined data of three individual mice per group of two independent experiments. * and #, P < 0.05; **, P < 0.01 for values significantly different from the controls (*) or SEA (#) based on paired analysis (one-sided paired Student's t test). ω-1, omega-1.
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fig6: Omega-1 is a major factor in SEA that conditions DCs for Th2 priming but not the only Th2-inducing component present in SEA. (A and B) Monocyte-derived DCs were pulsed for 48 h with 25 µg/ml SEA or 25 µg/ml omega-1–depleted SEA in combination with 100 ng/ml LPS and analyzed for surface expression of maturation markers and IL-12 production as described in the Fig. 2 legend. Error bars represent the mean ± SD of four independent experiments. (C) T cell–polarizing capacity of the conditioned DCs was evaluated as described in the Fig. 1 legend. Depicted are representative plots with percentages indicated. Based on intracellular cytokine staining, the ratio of T cells single positive for either IL-4 or IFN-γ was calculated relative to the control condition. Error bars represent the mean ± SD of five independent experiments. (D) 4get/KN2 mice were injected with recombinant proteins and analyzed as in Fig. 4. Depicted are representative plots with percentages indicated and the combined data of three individual mice per group of two independent experiments. * and #, P < 0.05; **, P < 0.01 for values significantly different from the controls (*) or SEA (#) based on paired analysis (one-sided paired Student's t test). ω-1, omega-1.

Mentions: Given the potency of omega-1 to condition DCs for Th2 priming in vitro and to drive Th2 polarization in vivo with similar characteristics as SEA, we depleted omega-1 from SEA (Fig. S3) to address the extent to which the Th2-polarizing capacity of SEA can be attributed to omega-1. Depletion of omega-1 almost completely abrogated the inhibitory effect of SEA on LPS-induced in vitro maturation (Fig. 6 A) and IL-12 cytokine production (Fig. 6 B) by DCs. Consistent with this observation, the Th2-polarizing capacity of omega-1–depleted SEA was also significantly reduced compared with whole SEA in the presence (Fig. 6 C) or absence of LPS (Fig. S4). This suggests that omega-1 is a principal factor in SEA mediating the conditioning of DCs for Th2 priming in vitro. In contrast, omega-1–depleted SEA was not impaired in its capacity to prime Th2 responses in vivo (Fig. 6 D). Thus, additional components in SEA are able to compensate for omega-1 with respect to Th2 priming in vivo. An interesting candidate could be the glycoprotein peroxiredoxin present in SEA, as this molecule has recently been shown to induce the development of alternatively activated macrophages (Donnelly et al., 2008), which may render it capable of initiating a Th2 response (Cua and Stohlman, 1997).


Omega-1, a glycoprotein secreted by Schistosoma mansoni eggs, drives Th2 responses.

Everts B, Perona-Wright G, Smits HH, Hokke CH, van der Ham AJ, Fitzsimmons CM, Doenhoff MJ, van der Bosch J, Mohrs K, Haas H, Mohrs M, Yazdanbakhsh M, Schramm G - J. Exp. Med. (2009)

Omega-1 is a major factor in SEA that conditions DCs for Th2 priming but not the only Th2-inducing component present in SEA. (A and B) Monocyte-derived DCs were pulsed for 48 h with 25 µg/ml SEA or 25 µg/ml omega-1–depleted SEA in combination with 100 ng/ml LPS and analyzed for surface expression of maturation markers and IL-12 production as described in the Fig. 2 legend. Error bars represent the mean ± SD of four independent experiments. (C) T cell–polarizing capacity of the conditioned DCs was evaluated as described in the Fig. 1 legend. Depicted are representative plots with percentages indicated. Based on intracellular cytokine staining, the ratio of T cells single positive for either IL-4 or IFN-γ was calculated relative to the control condition. Error bars represent the mean ± SD of five independent experiments. (D) 4get/KN2 mice were injected with recombinant proteins and analyzed as in Fig. 4. Depicted are representative plots with percentages indicated and the combined data of three individual mice per group of two independent experiments. * and #, P < 0.05; **, P < 0.01 for values significantly different from the controls (*) or SEA (#) based on paired analysis (one-sided paired Student's t test). ω-1, omega-1.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2722183&req=5

fig6: Omega-1 is a major factor in SEA that conditions DCs for Th2 priming but not the only Th2-inducing component present in SEA. (A and B) Monocyte-derived DCs were pulsed for 48 h with 25 µg/ml SEA or 25 µg/ml omega-1–depleted SEA in combination with 100 ng/ml LPS and analyzed for surface expression of maturation markers and IL-12 production as described in the Fig. 2 legend. Error bars represent the mean ± SD of four independent experiments. (C) T cell–polarizing capacity of the conditioned DCs was evaluated as described in the Fig. 1 legend. Depicted are representative plots with percentages indicated. Based on intracellular cytokine staining, the ratio of T cells single positive for either IL-4 or IFN-γ was calculated relative to the control condition. Error bars represent the mean ± SD of five independent experiments. (D) 4get/KN2 mice were injected with recombinant proteins and analyzed as in Fig. 4. Depicted are representative plots with percentages indicated and the combined data of three individual mice per group of two independent experiments. * and #, P < 0.05; **, P < 0.01 for values significantly different from the controls (*) or SEA (#) based on paired analysis (one-sided paired Student's t test). ω-1, omega-1.
Mentions: Given the potency of omega-1 to condition DCs for Th2 priming in vitro and to drive Th2 polarization in vivo with similar characteristics as SEA, we depleted omega-1 from SEA (Fig. S3) to address the extent to which the Th2-polarizing capacity of SEA can be attributed to omega-1. Depletion of omega-1 almost completely abrogated the inhibitory effect of SEA on LPS-induced in vitro maturation (Fig. 6 A) and IL-12 cytokine production (Fig. 6 B) by DCs. Consistent with this observation, the Th2-polarizing capacity of omega-1–depleted SEA was also significantly reduced compared with whole SEA in the presence (Fig. 6 C) or absence of LPS (Fig. S4). This suggests that omega-1 is a principal factor in SEA mediating the conditioning of DCs for Th2 priming in vitro. In contrast, omega-1–depleted SEA was not impaired in its capacity to prime Th2 responses in vivo (Fig. 6 D). Thus, additional components in SEA are able to compensate for omega-1 with respect to Th2 priming in vivo. An interesting candidate could be the glycoprotein peroxiredoxin present in SEA, as this molecule has recently been shown to induce the development of alternatively activated macrophages (Donnelly et al., 2008), which may render it capable of initiating a Th2 response (Cua and Stohlman, 1997).

Bottom Line: We report that omega-1, a glycoprotein which is secreted from S. mansoni eggs and present in SEA, is capable of conditioning human monocyte-derived dendritic cells in vitro to drive T helper 2 (Th2) polarization with similar characteristics as whole SEA.Finally, omega-1-depleted SEA displays an impaired capacity for Th2 priming in vitro, but not in vivo, suggesting the existence of additional factors within SEA that can compensate for the omega-1-mediated effects.Collectively, we identify omega-1, a single component of SEA, as a potent inducer of Th2 responses.

View Article: PubMed Central - PubMed

Affiliation: Department of Parasitology, Leiden University Medical Centre, Leiden 2333 ZA, The Netherlands.

ABSTRACT
Soluble egg antigens of the parasitic helminth Schistosoma mansoni (S. mansoni egg antigen [SEA]) induce strong Th2 responses both in vitro and in vivo. However, the specific molecules that prime the development of Th2 responses have not been identified. We report that omega-1, a glycoprotein which is secreted from S. mansoni eggs and present in SEA, is capable of conditioning human monocyte-derived dendritic cells in vitro to drive T helper 2 (Th2) polarization with similar characteristics as whole SEA. Furthermore, using IL-4 dual reporter mice, we show that both natural and recombinant omega-1 alone are sufficient to generate Th2 responses in vivo, even in the absence of IL-4R signaling. Finally, omega-1-depleted SEA displays an impaired capacity for Th2 priming in vitro, but not in vivo, suggesting the existence of additional factors within SEA that can compensate for the omega-1-mediated effects. Collectively, we identify omega-1, a single component of SEA, as a potent inducer of Th2 responses.

Show MeSH
Related in: MedlinePlus