Immunosuppression of TH2 responses in Trichinella spiralis infection by Helicobacter pylori neutrophil-activating protein

J Allergy Clin Immunol. 2008 Nov;122(5):908-913.e5. doi: 10.1016/j.jaci.2008.08.016. Epub 2008 Sep 19.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Bacterial / immunology
  • Bacterial Proteins / immunology*
  • Disease Models, Animal
  • Down-Regulation
  • Eosinophilia / immunology
  • Female
  • Immunoglobulin E / immunology
  • Interferon-gamma / immunology
  • Interleukin-12 / immunology
  • Interleukin-4 / immunology
  • Interleukin-5 / immunology
  • Mice
  • Mice, Inbred BALB C
  • Th1 Cells / immunology
  • Th2 Cells / immunology*
  • Trichinella spiralis*
  • Trichinellosis / immunology*

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • Interleukin-5
  • neutrophil-activating protein A, Helicobacter pylori
  • Interleukin-12
  • Interleukin-4
  • Immunoglobulin E
  • Interferon-gamma