Immunosuppression of TH2 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(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.


CONCLUSIONS
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.
Del Prete
Gianfranco
G
Department of Internal Medicine, University of Florence, Florence, Italy. gdelprete@unifi.it
Chiumiento
Lorena
L
Amedei
Amedeo
A
Piazza
Maria
M
D'Elios
Mario M
MM
Codolo
Gaia
G
de Bernard
Marina
M
Masetti
Massimo
M
Bruschi
Fabrizio
F
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D004802:Eosinophilia / Q000276:immunology; D005260:Female; D007073:Immunoglobulin E / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D017160:Trichinella spiralis; D014235:Trichinellosis / Q000276:immunology*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D015848:Interleukin-5; C092412:neutrophil-activating protein A, Helicobacter pylori; D018664:Interleukin-12; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma