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Natural Killer Cells andHelicobacter pyloriInfection: Bacterial Antigens and Interleukin-12 Act Synergistically To Induce Gamma Interferon Production
Author(s) -
CheolHeui Yun,
Anna Lundgren,
Josef Azem,
Åsa Sjöling,
Jan Holmgren,
AnnMari Svennerholm,
Björn Lundin
Publication year - 2005
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.73.3.1482-1490.2005
Subject(s) - interleukin 12 , biology , immune system , helicobacter pylori , lymphokine activated killer cell , interleukin 21 , antigen , interferon gamma , gastric mucosa , cytokine , immunology , microbiology and biotechnology , interleukin 2 , secretion , natural killer cell , janus kinase 3 , cytotoxic t cell , t cell , in vitro , stomach , biochemistry , genetics
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.

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