The neutrophil-activating protein of Helicobacter pylori promotes Th1 immune responses.
The Helicobacter pylori neutrophil-activating protein (HP-NAP) is a virulence factor of H. pylori that stimulates in neutrophils high production of oxygen radicals and adhesion to endothelial cells. We report here that HP-NAP is a TLR2 agonist able to induce the expression of IL-12 and IL-23 by neutrophils and monocytes. Addition in culture of HP-NAP, as an immune modulator, to antigen-induced T cell lines resulted in a remarkable increase in the number of IFN-gamma-producing T cells and decrease of IL-4-secreting cells, thus shifting the cytokine profile of antigen-activated human T cells from Th2 to a Th1 cytotoxic phenotype. We also found that in vivo HP-NAP elicited an antigen-specific Th1-polarized T cell response in the gastric mucosa of H. pylori-infected patients. These data indicate HP-NAP as an important factor of H. pylori able to elicit cells of the innate immune system to produce IL-12 and IL-23, and they suggest it as a new tool for promoting Th1 immune responses.
Department of Internal Medicine, University of Florence, Florence, Italy.
Amedeo
A
Amedei
Andrea
A
Cappon
Gaia
G
Codolo
Anna
A
Cabrelle
Alessandra
A
Polenghi
Marisa
M
Benagiano
Elisabetta
E
Tasca
Annalisa
A
Azzurri
Mario Milco
MM
D'Elios
Gianfranco
G
Del Prete
Marina
M
de Bernard
D000328:Adult; D000485:Allergens / Q000378:metabolism / Q000494:pharmacology; D001426:Bacterial Proteins / Q000378:metabolism* / Q000494:pharmacology; D015704:CD4 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism; D005260:Female; D005802:Genes, MHC Class II; D006098:Granulocytes / Q000378:metabolism; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D010641:Phenotype; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
D000485:Allergens; D001426:Bacterial Proteins; D015704:CD4 Antigens; C508840:IL23A protein, human; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; C092412:neutrophil-activating protein A, Helicobacter pylori; D018664:Interleukin-12; D007371:Interferon-gamma