The Journal of allergy and clinical immunology · 2008
Immunosuppression of TH2 responses in Trichinella spiralis infection by Helicobacter pylori neutrophil-activating protein.
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Del Prete Gianfranco, Chiumiento Lorena, Amedei Amedeo, Piazza Maria, D'Elios Mario M, Codolo Gaia, de Bernard Marina, Masetti Massimo, Bruschi Fabrizio
Аннотация
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(H)1 human allergen-specific T(H)2 cells in vitro.
OBJECTIVE: We performed an in vivo investigation of the ability of HP-NAP to downmodulate the T(H)2 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 microg 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-gamma plasma levels and lower IL-4 and IL-5 levels. The addition of anti-Toll-like receptor 2 antibody abrogated the anti-T(H)2/pro-T(H)1 activity of HP-NAP.
CONCLUSION: This study provides evidence that HP-NAP enhances endogenous IL-12 and IFN-gamma response and exerts a powerful anti-T(H)2 activity in vivo, targeting both IL-5-induced eosinophilia and IL-4-mediated hyper-IgE responses induced by parasitic infection.
OBJECTIVE: We performed an in vivo investigation of the ability of HP-NAP to downmodulate the T(H)2 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 microg 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-gamma plasma levels and lower IL-4 and IL-5 levels. The addition of anti-Toll-like receptor 2 antibody abrogated the anti-T(H)2/pro-T(H)1 activity of HP-NAP.
CONCLUSION: This study provides evidence that HP-NAP enhances endogenous IL-12 and IFN-gamma response and exerts a powerful anti-T(H)2 activity in vivo, targeting both IL-5-induced eosinophilia and IL-4-mediated hyper-IgE responses induced by parasitic infection.