Natural killer cells and Helicobacter pylori infection: bacterial antigens and interleukin-12 act synergistically to induce gamma interferon production.
Helicobacter pylori is known to induce a local immune response, which is characterized by activation of lymphocytes and the production of IFN-gamma in the stomach mucosa. Since not only T cells, but also natural killer (NK) cells, are potent producers of gamma interferon (IFN-gamma), 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-gamma 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-gamma 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 beta2. 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-gamma 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.
Yun
Cheol H
CH
Department of Medical Microbiology and Immunology and Göteborg University Vaccine Institute (GUVAX), Göteborg University, Box 435, 40530 Göteborg, Sweden.
Lundgren
Anna
A
Azem
Josef
J
Sjöling
Asa
A
Holmgren
Jan
J
Svennerholm
Ann-Mari
AM
Lundin
B Samuel
BS
D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology / Q000494:pharmacology*; D004357:Drug Synergism; D005753:Gastric Mucosa / Q000166:cytology / Q000276:immunology; D016481:Helicobacter Infections / Q000276:immunology* / Q000382:microbiology; D016480:Helicobacter pylori / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000276:immunology / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D008875:Middle Aged
D000942:Antigens, Bacterial; D018664:Interleukin-12; D007371:Interferon-gamma
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