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-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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adult
-
Allergens / metabolism
-
Allergens / pharmacology
-
Bacterial Proteins / metabolism*
-
Bacterial Proteins / pharmacology
-
CD4 Antigens / metabolism
-
Cells, Cultured
-
Dendritic Cells / metabolism
-
Female
-
Genes, MHC Class II
-
Granulocytes / metabolism
-
Helicobacter pylori / metabolism*
-
Humans
-
Immunity, Innate
-
Interferon-gamma / metabolism
-
Interleukin-12 / biosynthesis
-
Interleukin-23
-
Interleukin-23 Subunit p19
-
Interleukins / biosynthesis
-
Male
-
Middle Aged
-
Monocytes / metabolism
-
Neutrophils / metabolism
-
Phenotype
-
Th1 Cells / immunology*
-
Th1 Cells / metabolism
-
Time Factors
-
Toll-Like Receptor 2 / agonists
-
Toll-Like Receptor 2 / metabolism
-
Tumor Necrosis Factor-alpha / metabolism
-
Up-Regulation
Substances
-
Allergens
-
Bacterial Proteins
-
CD4 Antigens
-
IL23A protein, human
-
Interleukin-23
-
Interleukin-23 Subunit p19
-
Interleukins
-
TLR2 protein, human
-
Toll-Like Receptor 2
-
Tumor Necrosis Factor-alpha
-
neutrophil-activating protein A, Helicobacter pylori
-
Interleukin-12
-
Interferon-gamma