The neutrophil-activating protein of Helicobacter pylori promotes Th1 immune responses

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Abstract

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-γ–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.

Authors

Amedeo Amedei, Andrea Cappon, Gaia Codolo, Anna Cabrelle, Alessandra Polenghi, Marisa Benagiano, Elisabetta Tasca, Annalisa Azzurri, Mario Milco D’Elios, Gianfranco Del Prete, Marina de Bernard