Natural Killer Cells andHelicobacter pyloriInfection: Bacterial Antigens and Interleukin-12 Act Synergistically To Induce Gamma Interferon Production

Abstract

Helicobacter pylori is known to induce a local immune response, which is characterized by activation of lymphocytes and the production of IFN-␥ in the stomach mucosa. Since not only T cells, but also natural killer (NK) cells, are potent producers of gamma interferon (IFN-␥), we investigated whether NK cells play a role in the immune response to H. pylori infection. Our results showed that NK cells were present in both the gastric and duodenal mucosae but that H. pylori infection did not affect the infiltration of NK cells into the gastrointestinal area. Furthermore, we could show that NK cells could be activated directly by H. pylori antigens, as H. pylori bacteria, as well as lysate from H. pylori, induced the secretion of IFN-␥ by NK cells. NK cells were also activated without direct contact when separated from the bacteria by an epithelial cell layer, indicating that the activation of NK cells by H. pylori can also occur in vivo, in the infected stomach mucosa. Moreover, the production of IFN-␥ by NK cells was greatly enhanced when a small amount of interleukin-12 (IL-12) was added, and this synergistic effect was associated with increased expression of the IL-12 receptor ␤2. It was further evident that bacterial lysate alone was sufficient to induce the activation of cytotoxicity-related molecules. In conclusion, we demonstrated that NK cells are present in the gastroduodenal mucosa of humans and that NK cells produce high levels of IFN-␥ when stimulated with a combination of H. pylori antigen and IL-12. We propose that NK cells play an active role in the local immune response to H. pylori infection.

Helicobacter pylori Infection in a Pig Model Is Dominated by Th1 and Cytotoxic CD8+T Cell Responses

“…NK cells have been shown to secrete IFN-␥ upon stimulation with H. pylori lysate and IL-12 in vitro (57), which is attributed to recognition of the membrane-bound H. pylori lipoprotein HpaA by Toll-like receptor 2 (TLR2) (58). Lindgren et al (59) recently identified a subset of human CD8…”

MyD88-Dependent IFN-γ Production by NK Cells Is Key for Control ofLegionella pneumophilaInfection

“…NK cell-derived IFN-␥ has been shown to be critical in the resolution of other bacterial infections (51,52). In the context of Lpn infection, a critical role of IFN-␥ has been demonstrated (13,53).…”

Characterization of theHelicobacter pyloriCysteine-Rich Protein A as a T-Helper Cell Type 1 Polarizing Agent

“…Both HcpA and H. pylori mediate IFN-␥ production from naive splenocytes, which was shown to be suppressible by anti-IL-12 but not by anti-IL-2 antibodies. A possible role of NK cells in the observed IFN-␥ production (4,14,21) was substantiated by a very recent study by Yun et al (55), who demonstrated that a yet-unknown secreted factor from H. pylori, together with IL-12, was able to induce IFN-␥ production from human NK cells. Whether HcpA is involved in the activation of human or murine NK cells remains to be elucidated in future experiments.…”