Interferon-gamma secretion is induced in IL-12 stimulated human NK cells by recognition of Helicobacter pylori or TLR2 ligands

Helicobacter pylori induce a chronic inflammation in the human gastric mucosa characterized by increased production of interferon-gamma (IFN-gamma). The presence of natural killer (NK) cells in the human gastric mucosa and the ability of NK cells to produce IFN-gamma suggest an important role of NK cells in the immune response directed towards H. pylori infection. Since NK cells previously have been shown to respond to bacterial components with IFN-gamma production, we investigated the mechanisms for the recognition of H. pylori. We found that inhibition of MyD88 homodimerization resulted in decreased production of IFN-gamma and that inhibition of the p38 MAPK decreased the production as well as the secretion of IFN-gamma. Further studies indicated an involvement of Toll-like receptors (TLRs), in particular TLR2. Finally, we showed that the H. pylori specific membrane bound lipoprotein HpaA induced IFN-gamma production from NK cells through recognition by TLR2. In conclusion, we suggest an involvement of TLR2 in the recognition of H. pylori by human NK cells and that HpaA is a TLR2 ligand important for recognition.