Immunosuppression of T_H2 responses in Trichinella spiralis infection by Helicobacter pylori neutrophil-activating protein

Background

The Helicobacter pylori neutrophil-activating protein (HP-NAP) is able to induce IL-12 expression by cells of innate immunity and to shift to T_H1 human allergen-specific T_H2 cells in vitro.

Objective

We performed an in vivo investigation of the ability of HP-NAP to downmodulate the T_H2 response induced in mice by Trichinella spiralis infection.

Methods

Groups of T spiralis–infected BALB/c mice received intraperitoneal PBS/rat IgG2b (control animals) or 10 μg of HP-NAP with or without anti-Toll-like receptor 2 antibody on days 10 and 28 after infection. Blood eosinophils, total and T spiralis–specific IgE levels, and cytokine levels were measured in the plasma up to day 42, when splenocytes were cultured for cytokine production.

Results

Although control animals showed significant eosinophilia and increase of total and T spiralis–specific IgE, IL-4, and IL-5 levels from days 10 to 14, HP-NAP–treated animals showed less eosinophilia and total and excretory/secretory antigens of T spiralis–specific IgE in the blood. HP-NAP–treated animals also had higher IL-12 and IFN-γ plasma levels and lower IL-4 and IL-5 levels. The addition of anti-Toll-like receptor 2 antibody abrogated the anti-T_H2/pro-T_H1 activity of HP-NAP.

Conclusion

This study provides evidence that HP-NAP enhances endogenous IL-12 and IFN-γ response and exerts a powerful anti-T_H2 activity in vivo, targeting both IL-5–induced eosinophilia and IL-4–mediated hyper-IgE responses induced by parasitic infection.

Key words: T_H2 response, T_H2 immunosuppression, allergy, parasite infection, Trichinella spiralis, Helicobacter pylori neutrophil-activating protein, endogenous IL-12, mouse model, T_H1/T_H2 redirection

Abbreviations used: HP-NAP, Helicobacter pylori neutrophil-activating protein, Pam3, Lipohexapeptide tripalmitoyl-S-glyceryl-Cys-Ser-4(Lys), SEB, Staphylococcal enterotoxin B, TLR2, Toll-like receptor 2, TsE/S, Excretory/secretory antigens of Trichinella spiralis